Lori Muffly

All Publications

• Concordance of peripheral blood and bone marrow measurable residual disease in adult acute lymphoblastic leukemia. Blood advances Muffly, L., Sundaram, V., Chen, C., Yurkiewicz, I., Kuo, E., Burnash, S., Spiegel, J. Y., Arai, S., Frank, M. J., Johnston, L. J., Lowsky, R., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Sidana, S., Shiraz, P., Shizuru, J. A., Weng, W., Liedtke, M., Vempaty, H. T., Miklos, D. B. 2021; 5 (16): 3147-3151

  Abstract

  Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.

  View details for DOI 10.1182/bloodadvances.2021004234

  View details for PubMedID 34424318

• Decreased Early Mortality in Young Adult Patients With Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California JOURNAL OF ONCOLOGY PRACTICE Alvarez, E. M., Malogolowkin, M., Li, Q., Brunson, A., Pollock, B. H., Muffly, L., Wun, T., Keegan, T. M. 2019; 15 (4): 200-+

  View details for DOI 10.1200/JOP.18.00264

  View details for Web of Science ID 000467137600015

• Does Treatment Setting Matter? Evaluating Resource Utilization for Adolescents Treated in Pediatric vs Adult Cancer Institutions JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE Parsons, H. M., Muffly, L., Alvarez, E. M., Keegan, T. M. 2019; 111 (3): 224–25

  View details for DOI 10.1093/jnci/djy123

  View details for Web of Science ID 000467901100003

• Hematopoietic Cell Transplantation in Young Adult Acute Lymphoblastic Leukemia: A United States Population-Level Analysis. Journal of adolescent and young adult oncology Muffly, L., Li, Q., Alvarez, E., Kahn, J., Winestone, L., Cress, R., Penn, D. C., Keegan, T. H. 2019

  Abstract

  In this population-based evaluation of adolescents and young adults (AYA) acute lymphoblastic leukemia (ALL), we describe patterns of care (POC) and outcomes regarding hematopoietic cell transplantation (HCT) in first complete remission (CR1). Data were abstracted from the 2013 United States Surveillance, Epidemiology, and End Results POC study; newly diagnosed AYA ALL were included. Multivariable logistic regression evaluated associations with HCT in CR1; Cox proportional hazards regression evaluated survival associations. Of 399 AYAs with ALL included, 102 (28.5%) underwent HCT in CR1. High-risk cytogenetics (odds ratio [OR]=4.86, 95% confidence interval [CI]=3.02-7.83) and hyper-cyclophosphamide, vincristine, adriamycin, and dexamethasone (CVAD) induction (OR=1.84, 95% CI=1.07-3.16) were associated with HCT in CR1. Two-year cumulative incidence of relapse, relapse-free survival (RFS), and overall survival (OS) of the entire cohort were 28.3% (95% CI=23.4-33.4), 69.3% (95% CI=63.6-74.3%), and 84.1% (95% CI=79.7-87.5), respectively. Two-year RFS was significantly higher in patients receiving CR1 HCT relative to chemotherapy (83.6%, 95% CI=72.6-90.5% vs. 64.3%, 95% CI=57.5-70.3), but no difference was seen in 2-year OS (88.9%, 95% CI=80.8-93.7 vs. 82.5%, 95% CI=77.2-86.7). Treatment at a nonteaching hospital was independently associated with inferior OS (hazard ratio=2.15, 95% CI=1.23-3.76). Although the ALL landscape is changing, these data provide a snapshot of the use and outcomes of HCT for AYA ALL across the United States.

  View details for PubMedID 30657424

• Patterns of care and outcomes in adolescent and young adult acute lymphoblastic leukemia: a population-based study BLOOD ADVANCES Muffly, L., Alvarez, E., Lichtensztajn, D., Abrahao, R., Gomez, S., Keegan, T. 2018; 2 (8): 895–903

  Abstract

  Adolescents and young adults (AYAs, 15-39 years) with acute lymphoblastic leukemia (ALL) represent a heterogeneous population who receive care in pediatric or adult cancer settings. Using the California Cancer Registry, we describe AYA ALL patterns of care and outcomes over the past decade. Sociodemographics, treatment location, and front-line therapies administered to AYAs diagnosed with ALL between 2004 and 2014 were obtained. Cox regression models evaluated associations between ALL setting and regimen and overall survival (OS) and leukemia-specific survival (LSS) for the entire cohort, younger AYA (<25 years), and AYAs treated in the adult cancer setting only. Of 1473 cases, 67.7% were treated in an adult setting; of these, 24.8% received a pediatric ALL regimen and 40.7% were treated at a National Cancer Institute (NCI)-designated center. In multivariable analyses, front-line treatment in a pediatric (vs adult) setting (OS HR = 0.53, 95% confidence interval [CI], 0.37-0.76; LSS HR = 0.51, 95% CI, 0.35-0.74) and at an NCI/Children's Oncology Group (COG) center (OS HR = 0.80, 95% CI, 0.66-0.96; LSS HR = 0.80, 95% CI, 0.65-0.97) were associated with significantly superior survival. Results were similar when analyses were limited to younger AYAs. Outcomes for AYAs treated in an adult setting did not differ following front-line pediatric or adult ALL regimens. Our population-level findings demonstrate that two-thirds of AYAs with newly diagnosed ALL are treated in an adult cancer setting, with the majority receiving care in community settings. Given the potential survival benefits, front-line treatment of AYA ALL at pediatric and/or NCI/COG-designated cancer centers should be considered.

  View details for PubMedID 29669756

  View details for PubMedCentralID PMC5916002

• Adoption of Pediatric-Inspired Acute Lymphoblastic Leukemia Regimens by Adult Oncologists Treating Adolescents and Young Adults: A Population-Based Study CANCER Muffly, L., Lichtensztajn, D., Shiraz, P., Abrahao, R., McNeer, J., Stock, W., Keegan, T., Gomez, S. L. 2017; 123 (1): 122-130

  Abstract

  Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population-based description of ALL treatment patterns in AYA individuals over the past decade.Data regarding AYA patients aged 15 to 39 years and diagnosed with ALL between 2004 and 2014 while living in the Greater Bay Area were obtained from the Greater Bay Area Cancer Registry (GBACR). Treating facilities were designated as pediatric or adult centers; induction treatment regimens were abstracted from registry text data fields.Of 304 patients diagnosed in the GBACR catchment region, complete treatment data were available for 229 (75%). The location of care was identified for 296 patients (97%) treated at 31 unique centers. Approximately 70% of AYA patients received induction therapy at an adult treatment center. All AYA patients who were treated at pediatric centers received pediatric ALL regimens. Among AYA patients treated by adult oncologists with complete treatment data, none received a pediatric regimen before 2008. Between 2008 and 2012, while the US Adult Intergroup C10403 pediatric-inspired ALL protocol was open to accrual, 31% of AYA patients treated by adult oncologists received pediatric regimens. This rate fell to 21% from 2013 through 2014. Adult facilities treating ≥ 2 AYA patients with ALL per year captured in the GBACR were more likely to administer pediatric regimens than lower volume centers (P = .03).As of 2014, only a minority of AYA patients with ALL received pediatric ALL regimens at adult cancer centers. Cancer 2017;122-130. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30322

  View details for Web of Science ID 000394719100016

  View details for PubMedCentralID PMC5161602

• CAR19 monitoring by peripheral blood immunophenotyping reveals histology-specific expansion and toxicity. Blood advances Hamilton, M. P., Craig, E., Gentille Sanchez, C., Mina, A., Tamaresis, J., Kirmani, N., Ehlinger, Z., Syal, S., Good, Z., Sworder, B., Schroers-Martin, J., Lu, Y., Muffly, L., Negrin, R. S., Arai, S., Lowsky, R., Meyer, E., Rezvani, A. R., Shizuru, J. A., Weng, W. K., Shiraz, P., Sidana, S., Bharadwaj, S., Smith, M., Dahiya, S., Sahaf, B., Kurtz, D. M., Mackall, C. L., Tibshirani, R., Alizadeh, A. A., Frank, M. J., Miklos, D. B. 2024

  Abstract

  Chimeric antigen receptor (CAR) T cells directed against CD19 (CAR19) are a revolutionary treatment for B-cell lymphomas. CAR19 cell expansion is necessary for CAR19 function but is also associated with toxicity. To define the impact of CAR19 expansion on patient outcomes, we prospectively followed a cohort of 236 patients treated with CAR19 (brexucabtagene autoleucel or axicabtagene ciloleucel) for mantle cell (MCL), follicular (FL), and large B-cell lymphoma (LBCL) over the course of five years and obtained CAR19 expansion data using peripheral blood immunophenotyping for 188 of these patients. CAR19 expansion was higher in patients with MCL compared to other lymphoma histologic subtypes. Notably, patients with MCL had increased toxicity and required four-fold higher cumulative steroid doses than patients with LBCL. CAR19 expansion was associated with the development of cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), and the requirement for granulocyte colony stimulating factor (GCSF) after day 14 post-infusion. Younger patients and those with elevated lactate dehydrogenase (LDH) had significantly higher CAR19 expansion. In general, no association between CAR19 expansion and LBCL treatment response was observed. However, when controlling for tumor burden, we found that lower CAR19 expansion in conjunction with low LDH was associated with improved outcomes in LBCL. In sum, this study finds CAR19 expansion principally associates with CAR-related toxicity. Additionally, CAR19 expansion as measured by peripheral blood immunophenotyping may be dispensable to favorable outcomes in LBCL.

  View details for DOI 10.1182/bloodadvances.2024012637

  View details for PubMedID 38498731

• CD22 CAR T cells demonstrate high response rates and safety in pediatric and adult B-ALL: Phase 1b results. Leukemia Schultz, L. M., Jeyakumar, N., Kramer, A. M., Sahaf, B., Srinagesh, H., Shiraz, P., Agarwal, N., Hamilton, M., Erickson, C., Jacobs, A., Moon, J., Baggott, C., Arai, S., Bharadwaj, S., Johnston, L. J., Liedtke, M., Lowsky, R., Meyer, E., Negrin, R., Rezvani, A., Shizuru, J., Sidana, S., Egeler, E., Mavroukakis, S., Tunuguntla, R., Gkitsas-Long, N., Retherford, A., Brown, A. K., Gramstrap-Petersen, A. L., Ibañez, R. M., Feldman, S. A., Miklos, D. B., Mackall, C. L., Davis, K. L., Frank, M., Ramakrishna, S., Muffly, L. 2024

  Abstract

  Chimeric antigen receptor (CAR) T cells targeting CD22 (CD22-CAR) provide a therapeutic option for patients with CD22+ malignancies with progression after CD19-directed therapies. Using on-site, automated, closed-loop manufacturing, we conducted parallel Phase 1b clinical trials investigating a humanized CD22-CAR with 41BB costimulatory domain in children and adults with heavily treated, relapsed/refractory (r/r) B-ALL. Of 19 patients enrolled, 18 had successful CD22-CAR manufacturing, and 16 patients were infused. High grade (3-4) cytokine release syndrome (CRS) and immune effector-cell-associated neurotoxicity syndrome (ICANS) each occurred in only one patient; however, three patients experienced immune-effector-cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Twelve of 16 patients (75%) achieved CR with an overall 56% MRD-negative CR rate. Duration of response was overall limited (median 77 days), and CD22 expression was downregulated in 4/12 (33%) available samples at relapse. In summary, we demonstrate that closed-loop manufacturing of CD22-CAR T cells is feasible and is associated with a favorable safety profile and high CR rates in pediatric and adult r/r B-ALL, a cohort with limited CD22-CAR reporting.

  View details for DOI 10.1038/s41375-024-02220-y

  View details for PubMedID 38491306

  View details for PubMedCentralID 4993814

• Gilteritinib as Post-Transplant Maintenance for Acute Myeloid Leukemia With Internal Tandem Duplication Mutation of FLT3. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Levis, M. J., Hamadani, M., Logan, B., Jones, R. J., Singh, A. K., Litzow, M., Wingard, J. R., Papadopoulos, E. B., Perl, A. E., Soiffer, R. J., Ustun, C., Ueda Oshima, M., Uy, G. L., Waller, E. K., Vasu, S., Solh, M., Mishra, A., Muffly, L., Kim, H. J., Mikesch, J. H., Najima, Y., Onozawa, M., Thomson, K., Nagler, A., Wei, A. H., Marcucci, G., Geller, N. L., Hasabou, N., Delgado, D., Rosales, M., Hill, J., Gill, S. C., Nuthethi, R., King, D., Wittsack, H., Mendizabal, A., Devine, S. M., Horowitz, M. M., Chen, Y. B. 2024: JCO2302474

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with acute myeloid leukemia (AML) harboring an internal tandem duplication mutation of FLT3 (FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit.Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS.Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575).Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

  View details for DOI 10.1200/JCO.23.02474

  View details for PubMedID 38471061

• Utilization of Autologous Hematopoietic Cell Transplantation Over Time in Multiple Myeloma: A Population-Based Study. Clinical lymphoma, myeloma & leukemia Esteghamat, N. S., Brunson, A., Rosenberg, A. S., Schonfeld, S. J., Valcarcel, B., Abrahao, R., Cooley, J. J., Meyer, C. L., Auletta, J. J., Morton, L. M., Muffly, L., Wun, T., Keegan, T. H. 2023

  Abstract

  PURPOSE: Autologous hematopoietic cell transplantation (autoHCT) is associated with survival benefits in multiple myeloma (MM), but utilization remains low and differs by sociodemographic factors. Prior population-based studies have not fully captured autoHCT utilization or examined relationships between sociodemographic factors and autoHCT trends over time.PATIENTS AND METHODS: We used a novel data linkage between the California Cancer Registry, Center for International Blood and Marrow Transplant Research, and hospitalizations to capture autoHCT in a population-based MM cohort (n=29, 109; 1991-2016). Due to interactions by treatment era, stratified multivariable Cox proportional hazards regression models determined factors associated with autoHCT.RESULTS: The frequency of MM patients who received autoHCT increased from 5.7% (1991-1995) to 27.4% (2011-2016). In models by treatment era, patients with public/no (vs. private) health insurance were less likely to receive autoHCT (2011-2016 Medicare hazard ratio (HR) 0.70, 95% confidence interval (CI): 0.63-0.78; Medicaid HR 0.81, CI: 0.72-0.91; no insurance HR 0.56, CI: 0.32-0.99). In each treatment era, Black/African American (vs. non-Hispanic White) patients were less likely to receive autoHCT (2011-2016 HR 0.83, CI: 0.72-0.95). Hispanic patients were less likely to undergo autoHCT, most prominently in the earliest treatment era (1991-1995 HR 0.58, 95% CI: 0.37-0.90; 2011-2016 HR 1.07, CI: 0.96-1.19). Patients in lower socioeconomic status neighborhoods were less likely to utilize autoHCT, but differences decreased over time.CONCLUSIONS: Despite increases in autoHCT utilization, sociodemographic disparities remain. Identifying and mitigating barriers to autoHCT is essential to ensuring more equitable access to this highly effective therapy.

  View details for DOI 10.1016/j.clml.2023.12.009

  View details for PubMedID 38195324

• Single Center Randomized Trial of T-reg graft alone versus T-reg graft Plus Tacrolimus for the Prevention of Acute GVHD. Blood advances Bader, C. S., Pavlova, A., Lowsky, R., Muffly, L., Shiraz, P., Arai, S., Johnston, L. J., Rezvani, A. R., Weng, W. K., Miklos, D. B., Frank, M. J., Tamaresis, J. S., Agrawal, V., Bharadwaj, S., Sidana, S., Shizuru, J. A., Fernhoff, N. B., Putnam, A., Killian, S., Xie, B. J., Negrin, R. S., Meyer, E. 2023

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy for hematological malignancies for which graft-versus-host disease (GVHD) remains a major complication. The use of donor T regulatory cells (Tregs) to prevent GVHD appears promising, including in our previous evaluation of an engineered graft product (T-reg graft) consisting of the timed, sequential infusion of CD34+ hematopoietic stem cells and high-purity Tregs followed by conventional T cells. However, whether immunosuppressive prophylaxis can be removed from this protocol remains unclear. We report the results of the first stage of an open-label single-center phase 2 study (NCT01660607) investigating T-reg graft in myeloablative HCT of HLA-matched and 9/10 matched recipients. Twenty-four patients were randomized to receive T-reg graft alone (n=12) or T-reg graft plus single-agent GVHD prophylaxis (n=12) to determine if T-reg graft alone was non-inferior in preventing acute GVHD. All patients developed full donor myeloid chimerism. Patients with T-reg graft alone versus with prophylaxis had an incidence of grade II-IV acute GVHD of 58% versus 8% (p=0.005) and grade III-IV of 17% versus 0% (p=0.149), respectively. The incidence of moderate to severe chronic GVHD was 28% in the T-reg graft alone arm versus 0% with prophylaxis (p=0.056). Among patients with T-reg graft and prophylaxis, CD4+ T cell:Treg ratios were reduced after transplantation, gene-expression profiles showed reduced CD4+ proliferation, and the achievement of full donor T cell chimerism was delayed. This study indicates that T-reg graft with single-agent tacrolimus is preferred to T-reg graft alone for the prevention of acute GVHD. Clinical Trial #: NCT01660607.

  View details for DOI 10.1182/bloodadvances.2023011625

  View details for PubMedID 38091578

• Comparison of vital status, cause of death, and follow-up after HCT in linked CIBMTR and California Cancer Registry data, 1991-2018. Transplantation and cellular therapy Valcarcel, B., Schonfeld, S. J., Meyer, C. L., Brunson, A., Cooley, J. J., Abrahão, R., Wun, T., Auletta, J. J., Gadalla, S. M., Engels, E., Albert, P. S., Spellman, S. R., Rizzo, J. D., Shaw, B. E., Muffly, L., Keegan, T. H., Morton, L. M. 2023

  Abstract

  Assessing outcomes following hematopoietic cell transplantation (HCT) poses challenges due to the necessity for systematic and often prolonged patient follow-up. Linking the HCT database of the Center for International Blood and Marrow Transplant Research (CIBMTR) with cancer registry data may improve long-term outcome ascertainment, but the reliability of mortality data in death certificates from cancer registries among HCT recipients remains unknown.We compared the classification of vital status and primary cause of death (COD), as well as the length of follow-up between the CIBMTR and California Cancer Registry (CCR) to assess the feasibility of supplementing the CIBMTR with cancer registry data.This retrospective study leveraged a linked CIBMTR-CCR dataset. We included patients who were California residents at the time of HCT and received a first allogeneic (alloHCT) or autologous (autoHCT) HCT for a hematologic malignancy diagnosed during 1991-2016. Follow-up was through 2018.We analyzed 18,450 patients (alloHCT, n=8,232; autoHCT, n=10,218). Vital status agreement was 97.7% for alloHCT and 97.2% for autoHCT. Unknown COD was higher in CIBMTR (12.9%) than CCR (1.6%). After excluding patients with unknown COD information, the overall agreement of primary COD (cancer vs. noncancer) was 53.7% for alloHCT and 83.2% for autoHCT. This agreement was lower within the first 100 days following HCT (alloHCT=31.0%, autoHCT=54.6%). Compared with CIBMTR, deaths due to cancer were higher in CCR (alloHCT=90.0%, autoHCT=90.1% vs. alloHCT=47.3%, autoHCT=82.5% in CIBMTR). CIBMTR reports more frequently noncancer-related deaths, including graft-versus-host disease and infections. Cumulative incidence of cancer-specific mortality at 20 years differed particularly for alloHCT (CCR=53.7%, CIBMTR=27.6%). Median follow-up among alive patients was longer in CCR (alloHCT=6.0, autoHCT=4.7 years) than in CIBMTR (alloHCT=5.0, autoHCT=3.8 years).Our findings highlight the completeness of vital status data in CIBMTR but reveal substantial disagreement in primary COD. Consequently, caution is required when interpreting HCT studies that only use death certificates to estimate cause-specific mortality outcomes. Improving the accuracy of COD registration and follow-up completeness by developing communication pathways between cancer registries and hospital-based cohorts may enhance our understanding of late effects and long-term outcomes among HCT survivors.

  View details for DOI 10.1016/j.jtct.2023.11.011

  View details for PubMedID 37981238

• CAR19 Therapy Drives Expansion of Clonal Hematopoiesis and Associated Cytopenias Hamilton, M. P., Sworder, B. J., Alig, S. K., Good, Z., Boegeholz, J., Schroers-Martin, J., Tamaresis, J., Esfahani, M., Lu, Y., Olsen, M., Liu, C., Ehlinger, Z., Desai, M., Liu-Fei, F., Muffly, L. S., Negrin, R. S., Arai, S., Johnston, L., Lowsky, R., Meyer, E. H., Rezvani, A. R., Shizuru, J., Weng, W., Shiraz, P., Sidana, S., Bharadwaj, S., Smith, M., Dahiya, S., Sahaf, B., Diehn, M., Frank, M. J., Mackall, C. L., Kurtz, D. M., Miklos, D. B., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182522

  View details for Web of Science ID 001159306701117

• Final Results from Phase 1 Study of Briquilimab, an Anti-CD117 Monoclonal Antibody, in Combination with Low Dose Irradiation and Fludarabine Conditioning, Shows Durable Remissions in Older Adults with Acute Myeloid Leukemia in Complete Remission and Myelodysplastic Syndrome Undergoing Allogeneic Hematopoietic Cell Transplantation Gandhi, A., Artz, A., Lee, C. J., Varma, A., Scott, B. L., Kwon, H., Youn, M., Yanagiba, C., Arulprakasam, J., Le, A., Shizuru, J., Pang, W. W., Muffly, L. S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185533

  View details for Web of Science ID 001159306701227

• Update for the 'Watch' Registry, a Real-World Observational Study Using Clonoseq® to Monitor MRD in Lymphoid Malignancies Cowan, A. J., Patel, K., Svoboda, J., Shah, B. D., Cheson, B. D., Azzi, G., Rabara, V., Muffly, L. S., Simmons, H., Thuillier, S., Leonard, J. T. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187586

  View details for Web of Science ID 001159740305123

• Bridging Therapy in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Receiving Standard of Care Brexucabtagene Autoleucel: Results from the RealWorld Outcomes Collaborative of CAR T in Adult ALL (ROCCA) Lin, C., Tsai, S. B., Roloff, G. W., Zhang, A., Aldoss, I., Kopmar, N. E., Dekker, S. E., Jeyakumar, N., Gupta, V. K., O'Connor, T. E., Dykes, K. C., Ahmed, M., Dholaria, B., Zambrano, H., Bradshaw, D., Logan, A. C., Tracy, S., Kubiak, M., Solh, M. M., Mercadal, S., Schwartz, M., Mukherjee, A., Battiwalla, M., Shaughnessy, P., Majhail, N., Mountjoy, L., Malik, S. A., Mathews, J., Ladha, A., Advani, A. S., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., O'Dwyer, K. M., Sasine, J., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Oliai, C. H., Bachanova, V., Stock, W., Pullarkat, V., Cassaday, R. D., Miller, K., Muffly, L. S., Galal, A., Shah, B. D., Faramand, R. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182380

  View details for Web of Science ID 001159740304113

• The Impact of Inotuzumab Ozogamicin (InO) Treatment on Brexucabtagene Autoleucel (Brexu-cel) Outcomes in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (B-ALL) Aldoss, I., Roloff, G. W., Advani, A. S., Kopmar, N. E., Lin, C., Dekker, S. E., Gupta, V. K., Jeyakumar, N., O'Connor, T. E., Zhang, A., Miller, K., Dykes, K. C., Ahmed, M., Zambrano, H., Bradshaw, D., Mercadal, S., Schwartz, M., Tracy, S., Dholaria, B., Kubiak, M., Mukherjee, A., Majhail, N., Battiwalla, M., Mountjoy, L., Malik, S. A., Mathews, J., Shaughnessy, P., Logan, A. C., Ladha, A., Yaghmour, G., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., O'Dwyer, K. M., Tsai, S. B., Sasine, J., Solh, M. M., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Oliai, C. H., Bachanova, V., Stock, W., Galal, A., Pullarkat, V., Cassaday, R. D., Shah, B. D., Faramand, R., Muffly, L. S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182404

  View details for Web of Science ID 001159900800078

• Discordance between Next Generation Sequencing and BCR-ABL PCR Measurable Residual Disease in Adult Patients with Ph plus Acute Lymphoblastic Leukemia Dekker, S. E., Sabile, J., Dasilva, B., Saygin, C., Schwartz, M., Raman, H. S., Kaempf, A., Luskin, M. R., Patel, A., Muffly, L. S., Leonard, J. T. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185040

  View details for Web of Science ID 001159900804029

• Phase 1/2 Study of Donor-Derived Anti-CD33 Chimeric Antigen Receptor Expressing T Cells (VCAR33) in Patients with Relapsed or Refractory Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation Shah, N. N., Azzi, J., Cooper, B. W., Deol, A., DiPersio, J., Koura, D., McClune, B., Muffly, L. S., Mushtaq, M., Narayan, R., Suh, H., Yanik, G., Nath, S., Whangbo, J., Koehne, G. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-180990

  View details for Web of Science ID 001159900800063

• The Impact of Social Determinants of Health on Brexucabtagene Autoleucel Outcomes in Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia O'Connor, T. E., Lin, C., Roloff, G. W., Zhang, A., Aldoss, I., Faramand, R., Kopmar, N. E., Dykes, K. C., Jeyakumar, N., Dekker, S. E., Gupta, V. K., Ahmed, M., Logan, A. C., Zambrano, H., Bradshaw, D., Mercadal, S., Schwartz, M., Tracy, S., Kubiak, M., Mukherjee, A., Majhail, N., Battiwalla, M., Mountjoy, L., Malik, S., Mathews, J., Shaughnessy, P., Ladha, A., Yaghmour, G., Advani, A. S., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., Sasine, J., Solh, M. M., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Oliai, C. H., Bachanova, V., Stock, W., Cassaday, R. D., Shah, B. D., Miller, K., Muffly, L. S., Galal, A., Tsai, S. B., Dholaria, B. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182566

  View details for Web of Science ID 001159306702183

• Toxicity Profile of Brexucabtagene Autoleucel (brexu-cel; CD19-directed CAR T-cell therapy) in Adult Patients (pts) with Relapsed/Refractory (R/R) B-Cell Acute Lymphoblastic Leukemia (B-ALL): Results from a Multicenter Real-World Outcomes Study Kopmar, N. E., Gooley, T., Roloff, G. W., Aldoss, I., Lin, C., Dekker, S. E., Gupta, V. K., Jeyakumar, N., O'connor, T., Dykes, K. C., Ahmed, M., Zambrano, H., Bradshaw, D., Mercadal, S., Schwartz, M., Tracy, S., Dholaria, B., Kubiak, M., Mukherjee, A., Majhail, N., Battiwalla, M., Mountjoy, L., Malik, S., Shaughnessy, P., Mathews, J., Logan, A. C., Ladha, A., Yaghmour, G., Advani, A. S., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., O'Dwyer, K. M., Tsai, S. B., Sasine, J., Solh, M. M., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Oliai, C. H., Bachanova, V., Stock, W., Galal, A., Pullarkat, V., Shah, B. D., Faramand, R., Muffly, L. S., Cassaday, R. D. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185107

  View details for Web of Science ID 001159306702035

• Age-Related Differences in Utilization of Allogeneic HCT for Acute Myeloid Leukemia in California: Results of a Population-Based, Novel Linked Dataset Meyer, C. L., Keegan, T. M., Brunson, A., Auletta, J. J., Morton, L. M., Wun, T., Schonfeld, S. J., Valcarcel, B., Abrahao, R., Yusuf, R., Muffly, L. S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-179457

  View details for Web of Science ID 001159306701018

• Impact of Prior Response to Blinatumomab on Outcomes of Brexucabtagene Autoleucel (Brexu-cel) in Adult Patients with Relapsed or Refractory (r/r) B-Cell Acute Lymphoblastic Leukemia (B-ALL): Results from the Real-World Outcomes Collaborative of CAR-T in Adult ALL (ROCCA) Gupta, V. K., Roloff, G. W., Muffly, L. S., Aldoss, I., Kopmar, N. E., Lin, C., Dekker, S. E., Jeyakumar, N., O'Connor, T. E., Zhang, A., Miller, K., Dykes, K. C., Ahmed, M., Bradshaw, D., Mercadal, S., Schwartz, M., Tracy, S., Dholaria, B., Kubiak, M., Mukherjee, A., Majhail, N., Battiwalla, M., Mountjoy, L., Malik, S., Mathews, J., Shaughnessy, P., Logan, A. C., Ladha, A., Yaghmour, G., Advani, A. S., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., O'Dwyer, K. M., Tsai, S. B., Sasine, J., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Stock, W., Galal, A., Pullarkat, V., Cassaday, R. D., Shah, B. D., Faramand, R., Oliai, C. H. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182915

  View details for Web of Science ID 001159306708092

• Brexucabtagene Autoleucel in Adults with Relapsed/ Refractory B-Cell ALL: Outcomes and Novel Insights from the Real-World Outcomes Collaborative of CAR T in Adult ALL (ROCCA) Roloff, G. W., Aldoss, I., Kopmar, N. E., Lin, C., Dekker, S. E., Gupta, V. K., Jeyakumar, N., O'Connor, T. E., Zhang, A., Miller, K., Dykes, K. C., Ahmed, M., Zambrano, H., Bradshaw, D., Mercadal, S., Schwartz, M., Tracy, S., Dholaria, B., Kubiak, M., Mukherjee, A., Majhail, N., Battiwalla, M., Mountjoy, L., Malik, S. A., Mathews, J., Shaughnessy, P., Logan, A. C., Ladha, A., Yaghmour, G., Advani, A. S., Stefan, M., Guzowski, C., Hoeg, R. T., Hilal, T., Moore, J., O'Dwyer, K. M., Tsai, S. B., Sasine, J., Solh, M. M., Lee, C. J., Kota, V. K., Koura, D., Veeraputhiran, M., Blunk, B., Leonard, J. T., Bachanova, V., Stock, W., Galal, A., Pullarkat, V., Cassaday, R. D., Shah, B. D., Faramand, R., Muffly, L. S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-182531

  View details for Web of Science ID 001159306704054

• Post-Hoc Analysis of Measurable Residual Disease from BMT-CTN 1506/Morpho: FLT3ITD Variant Allele Frequency and Survival Are Highly Correlated Levis, M. J., Hamadani, M., Logan, B. R., Jones, R. J., Singh, A. K., Litzow, M. R., Wingard, J. R., Papadopoulos, E. B., Perl, A., Soiffer, R. J., Ustun, C., Oshima, M., Uy, G. L., Waller, E. K., Vasu, S., Solh, M. M., Mishra, A., Muffly, L. S., Kim, H., Stelljes, M., Najima, Y., Onozawa, M., Thomson, K., Nagler, A., Wei, A. H., Marcucci, G., Hasabou, N., Rosales, M., Hill, J., Gill, S. C., Nuthethi, R., King, D., Wittsack, H., Mendizabel, A., Devine, S. M., Horowitz, M. M., Chen, Y. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-177929

  View details for Web of Science ID 001159306703242

• Retrospective Analysis of Adolescent Young Adult Patients with Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma Treated with the CALGB 10403 Regimen Since Completion of Trial Enrollment DaSilva, B., Vyas, R. D., Darwin, A., Russel, K., Gilbert, J., Tan, V., Darji, H., Miller, K., Liang, E. C., Raychaudhuri, S., Duvall, A. S., Liedtke, M., Stock, W., Cassaday, R., Schwartz, M., Leonard, J. T., Luskin, M. R., Muffly, L. S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185176

  View details for Web of Science ID 001159740306286

• CD22 CAR T Cell-Related IEC-HS Is Associated with an IFN-. Cytokine Signature Srinagesh, H., Baird, J. H., Agarwal, N., Su, Y., Kramer, A., Reschke, A., Jeyakumar, N., Bharadwaj, S., Schultz, L., Ramakrishna, S., Davis, K. L., Sahaf, B., Feldman, S., Mackall, C. L., Miklos, D. B., Muffly, L. S., Frank, M. J. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-178283

  View details for Web of Science ID 001159900800040

• Manufacturing of a Subsequent Autologous CAR-T Product after Prior CAR-T Is Safe and Feasible Su, Y., Kramer, A., Hamilton, M. P., Agarwal, N., Feldman, S., Sahaf, B., Kuo, A., Mackall, C. L., Muffly, L. S., Miklos, D. B., Frank, M. J. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-185413

  View details for Web of Science ID 001159306704061

• Transcriptional Profiling Associated with CD22 CAR T Cell Clinical Response in LBCL Kramer, A., Hamilton, M. P., Prabhu, S., Desai, M., Kuo, A., Ehlinger, Z., Agarwal, N., Su, Y., Gkitsas, N., Fowler, C., Keerthi, V., Retherford, A., Klysz, D., Tunuguntla, R., Feldman, S., Sahaf, B., Baird, J. H., Muffly, L. S., Mackall, C. L., Miklos, D. B., Good, Z., Frank, M. J. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187615

  View details for Web of Science ID 001159306708064

• Phase 1 Trial Results for Patients with Advanced Hematologic Malignancies Undergoing Reduced Intensity Allogeneic HCT with Orca-T Donor Cell Therapy Product and Single Agent Tacrolimus Villar-Prados, A., Meyer, E. H., Sutherland, K., Negrin, R. S., Arai, S., Frank, M. J., Johnston, L., Lowsky, R., Miklos, D. B., Muffly, L. S., Dahiya, S., Rezvani, A. R., Sidana, S., Shiraz, P., Shizuru, J., Weng, W., Smith, M., Bharadwaj, S., Tamaresis, J., Pavlova, A., McClellan, S. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-188162

  View details for Web of Science ID 001159740304171

• Optimizing Outcomes with Myeloablative Conditioning in Older Patients: Efficacy and Safety of Precision Engineered Orca-T in Patients > 55 Years Old with Hematologic Malignancies Oliai, C. H., Pantin, J. M., Hoeg, R. T., Muffly, L. S., Patel, S. S., Gandhi, A., Lowsky, R., Salhotra, A., Dholaria, B., Waller, E. K., Srour, S. A., Pavlova, A., Fernhoff, N. B., Agodoa, I., McClellan, J., Abedi, M., Negrin, R. S., Meyer, E. H. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-186749

  View details for Web of Science ID 001159306700231

• PRECISION-ENGINEERED CELL THERAPY ORCA-T DEMONSTRATES HIGH RELAPSE-FREE SURVIVAL AT 1 YEAR WHILE REDUCING GRAFT-VERSUS-HOST DISEASE AND TOXICITY Oliai, C., Hoeg, R., Pavlova, A., Gandhi, A., Muffly, L., Mehta, R., Srour, S., Waller, E., Lowsky, R., Patel, S., Dholaria, B., Pantin, J., Salhotra, A., Fernhoff, N., McClellan, J., Abedi, M., Negrin, R., Meyer, E. SPRINGERNATURE. 2023: 230-231

  View details for Web of Science ID 001110902800293

• SOCIAL FUNCTIONING AFTER TRANSPLANTATION AND CELLULAR THERAPY: INITIAL PATIENT-REPORTED OUTCOMES RESULTS FROM THE CIBMTR Cusatis, R., Ndifon, E., Mattila, D., Berman, L., Akinola, I., Kapfhammer, M., Jacox, C., Luetke, C., Hamilton, B., Muffly, L., Shaughnessy, P., Shaw, B., Flynn, K. SPRINGERNATURE. 2023: 700

  View details for Web of Science ID 001110902800992

• GVHD ASSESSMENT IN PHASE 1 STUDY OF BRIQUILIMAB (JSP191), LOW DOSE IRRADIATION AND FLUDARABINE CONDITIONING IN OLDER ADULTS WITH MDS/AML UNDERGOING ALLOGENEIC HCT Youn, M., Muffly, L., Artz, A., Lee, C., Gandhi, A., Varma, A., Scott, B., Yanagiba, C., Tiwari, R., Arulprakasam, J., Le, A., Shizuru, J., Kwon, H., Pang, W. SPRINGERNATURE. 2023: 306-307

  View details for Web of Science ID 001110902800399

• Impact of Specialized Treatment Setting on Survival in Adolescent and Young Adult ALL. JCO oncology practice Muffly, L. S., Parsons, H. M., Miller, K., Li, Q., Brunson, A., Keegan, T. H. 2023: OP2300373

  Abstract

  Unlike children with ALL who receive cancer care primarily at specialized cancer centers (SCCs; National Cancer Institute and/or Children's Oncology Group centers), adolescents and young adults (AYAs; 15-39 years) receive care in a variety of settings. Using population-based data, we describe where AYAs with ALL receive treatment and determine associations with overall survival (OS).Data from the 2004 to 2018 California (CA, n = 2,283), New York (NY, n = 795), and Texas (TX, n = 955) state cancer registries were used to identify treatment setting of AYAs with newly diagnosed ALL. Multivariable Cox proportional hazards regression models evaluated associations with OS.Seventy percent were older than 18 years, and 65% were male. A majority in CA (63%) and TX (64%) were Hispanic while most in NY were non-Hispanic White (50%). Treatment at an SCC occurred in 48.2% (CA), 44.4% (NY), and 19.5% (TX). Across states, AYAs who were older or uninsured were less likely to receive treatment at an SCC. Treatment at an SCC was associated with superior OS in CA (hazard ratio [HR], 0.73; 95% CI, 0.63 to 0.85) and TX (HR, 0.61; 95% CI, 0.45 to 0.83); a nonsignificant association was seen in NY (HR, 0.83; 95% CI, 0.64 to 1.08).Only 20%-50% of AYA patients with ALL received frontline treatment at SCCs. Treatment of ALL at an SCC was associated with superior survival, highlighting the importance of policy efforts to improve access and reduce inequities in AYA ALL care.

  View details for DOI 10.1200/OP.23.00373

  View details for PubMedID 37890123

• Bendamustine vs. fludarabine/cyclophosphamide lymphodepletion prior to BCMA CAR-T cell therapy in multiple myeloma. Blood cancer journal Sidana, S., Hosoya, H., Jensen, A., Liu, L., Goyal, A., Hovanky, V., Sahaf, B., Bharadwaj, S., Latchford, T., Arai, S., Leahy, S., Mei, M., Budde, L. E., Muffly, L. S., Frank, M. J., Dahiya, S., Htut, M., Miklos, D., Janakiram, M. 2023; 13 (1): 158

  View details for DOI 10.1038/s41408-023-00929-0

  View details for PubMedID 37833271

  View details for PubMedCentralID PMC10576036

• INSPIRED Symposium Part 4A: Access to CAR T cell Therapy in Unique Populations with B-cell Acute Lymphoblastic Leukemia. Transplantation and cellular therapy Winestone, L. E., Bhojwani, D., Ghorashian, S., Muffly, L., Leahy, A. B., Chao, K., Steineck, A., Rossig, C., Lamble, A., Maude, S. L., Myers, R., Rheingold, S. R. 2023

  Abstract

  Tisagenlecleucel's approval in children with B-cell acute lymphoblastic leukemia (B-ALL) was based on the phase 2 ELIANA trial, a global registration study. The ELIANA trial, however, excluded specific subsets of patients facing unique challenges and did not include enough patients to adequately evaluate outcomes in rare sub-populations. Since commercialization of tisagenlecleucel, data has become available that supports therapeutic indications beyond the specific cohorts previously eligible for Chimeric Antigen receptor targeted to CD19 (CD19 CAR) cell therapy on the registration clinical trial. Substantial real-world data and aggregate clinical trial data have addressed gaps in our understanding of response rates, longer-term efficacy, and toxicities associated with CD19 CAR T cells in special populations and rare clinical scenarios. This includes patients with central nervous system-relapsed disease, as they were excluded from ELIANA and other early CAR T cell trials due to concerns about risk of neurotoxicity that have not been born out. There is also interest in the use of CD19 CAR T cells for very high risk patients earlier in the course of therapy, such as patients with persistent minimal residual disease after two cycles of upfront chemotherapy and patients with first relapse of B-ALL. However, these indications are not part of the label for tisagenlecleucel and were historically not included in eligibility criteria for most clinical trials; data addressing these populations is needed. Populations at high risk of relapse, including patients with high-risk cytogenetic lesions, infants with B-ALL, patients with trisomy 21, and young adults with B-ALL may also benefit from earlier treatment with CD19 CAR T cell therapy. It is important to prospectively study patient-reported outcomes given the differential toxicity expected between CD19 CAR T cell therapy and the historic standard of care, hematopoietic cell transplant. Now that CD19 CAR T cell therapy is commercially available, studies evaluating potential access disparities created by this very expensive novel therapy are increasingly pressing.

  View details for DOI 10.1016/j.jtct.2023.10.005

  View details for PubMedID 37821078

• Clinical Outcomes and Treatment Patterns in Adult Patients With FMS-Like Tyrosine Kinase 3 Internal Tandem Duplication Positive Acute Myeloid Leukemia Undergoing Allogeneic Hemopoietic Cell Transplantation in the US and Canada: CIBMTR® (Center for International Blood and Marrow Transplant Research Analysis) Burns, L. J., Pandya, B. J., Chen, K., Wang, T., Xie, B., Touya, M., Spalding, J., Block, A., Kuperman, G., Young, C., Muffly, L. CIG MEDIA GROUP, LP. 2023: S276

  View details for Web of Science ID 001062479600147

• Precision-Engineered Cell Therapy Orca-T Demonstrates High Relapse-Free Survival at 1 Year While Reducing Graft-Versus-Host Disease (GvHD) and Toxicity Salhotra, A., Oliai, C., Hoeg, R. T., Gandhi, A., Muffly, L., Srour, S. A., Waller, E., Lowsky, R., Patel, S., Pantin, J., Dholaria, B., Pavlova, A., Fernhoff, N., Scott, J., Abedi, M., Negrin, R., Meyer, E. CIG MEDIA GROUP, LP. 2023: S316-S317

  View details for Web of Science ID 001062479600222

• Implementation of a Pilot Clinic for Pediatric to Adult Cancer Survivorship Transitions. Journal of adolescent and young adult oncology Jin, A. H., Simon, P. J., Clayton, A., Benedict, C., Liedtke, M., Muffly, L., Schapira, L., Smith, S. M. 2023

  Abstract

  Childhood cancer survivors are recommended to have lifelong survivorship care, yet many become disengaged during pediatric to adult care transitions. We implemented a pilot clinic for adult survivors of pediatric or adolescent and young adult (AYA) leukemia transitioning to adult-focused survivorship care. The clinic featured AYA-specific care, bidirectional communication with primary care, and a quality improvement (QI) cycle. During the 1-year QI period, 27 patients were seen and 21 completed postvisit interviews. The clinic was positively received by patients and primary care providers, showed promise for improving self-management and care coordination, and highlighted the need for novel approaches to connect survivors with primary care.

  View details for DOI 10.1089/jayao.2023.0041

  View details for PubMedID 37615593

• Healthcare resource utilization and costs during first salvage therapy for relapsed or refractory acute myeloid leukemia in the United States. Leukemia & lymphoma Muffly, L., Young, C., Feng, Q., Nimke, D., Pandya, B. J. 2023: 1-8

  Abstract

  Real-world US healthcare resource utilization (HRU) and costs during first salvage therapy for relapsed/refractory (R/R) acute myeloid leukemia (AML) are described using IBM MarketScan® data (1/1/2007-6/30/2020). Treatments included high- (HIC) and low-intensity chemotherapy (LIC) alone, and gilteritinib, other FLT3 tyrosine kinase inhibitors (TKIs), and venetoclax with or without chemotherapy. Patients were diagnosed with R/R AML at ≥18 years of age between 1/1/2017-12/31/2019. Patient monthly all-cause HRU and costs were analyzed using a fixed-effects model. Data from 399 patients were analyzed (HIC, n = 104; LIC, n = 133; gilteritinib, n = 14; other FLT3 TKIs, n = 68; venetoclax, n = 80). Inpatient HRU was generally highest with HIC, whereas outpatient HRU was generally highest with LIC and venetoclax. Total all-cause incremental monthly costs appeared to be highest with HIC ($171,982) and similar for LIC ($60,512), gilteritinib ($47,218), other FLT3 TKIs ($43,218), and venetoclax ($77,566). Results highlight HRU and cost differences for R/R AML during first salvage therapy.

  View details for DOI 10.1080/10428194.2023.2235044

  View details for PubMedID 37486091

• Specialty cancer care and survival in AYA ALL: A US multi-state analysis. Muffly, L. S., Miller, K., Maguire, F., Li, Q., Parsons, H. M., Keegan, T. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003380

• Outcomes following brexucabtagene autoleucel administered as an FDA-approved therapy for adults with relapsed/refractory B-ALL. Roloff, G., Faramand, R., Aldoss, I., Kopmar, N., Schwartz, M., Dekker, S. E., Lin, C., Tracy, S., Vilchez, S., Dykes, K., O'Connor, T., Ahmed, M., Gupta, V. K., Ladha, A., Tsai, S., Leonard, J., Galal, A., Cassaday, R., Shah, B. D., Muffly, L. S. LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772003373

• Next-Generation Sequencing-Based MRD in Adults with ALL Undergoing Hematopoietic Cell Transplantation. Blood advances Liang, E. C., Dekker, S. E., Sabile, J. M., Torelli, S., Zhang, A., Miller, K., Shiraz, P., Hayes-Lattin, B., Leonard, J. T., Muffly, L. 2023

  Abstract

  Measurable residual disease (MRD) is an adverse prognostic factor in adult acute lymphoblastic leukemia (ALL) patients undergoing hematopoietic cell transplantation (HCT). Next-generation sequencing (NGS) can detect MRD with a sensitivity of 10-6, but the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT remains minimally studied. To evaluate the prognostic value of NGS-based MRD in adult ALL patients undergoing HCT. Patients with ALL aged ≥18 years old who underwent allogeneic HCT at Stanford University or Oregon Health & Science University between January 2014-April 2021 and who were evaluated for MRD using the NGS-based clonoSEQ assay were included in this study. MRD was assessed pre-HCT (MRDpre) and for up to 1 year post-HCT (MRDpost). Patients were followed for leukemia relapse and survival for up to 2 years post-HCT. 158 patients had a trackable clonotype for MRD monitoring. The cumulative incidence of relapse was increased at all levels of MRDpre, including in patients who had low MRDpre of <10-4 (HR 3.56, 95% CI, 1.39-9.15). In multivariable analysis, MRDpre level remained significantly prognostic; however, detectable MRDpost was the strongest predictor of relapse (HR 4.60, 95% CI, 3.01-7.02). In exploratory analyses limited to B-cell ALL patients, detection of post-HCT IgH MRD clonotypes, rather than non-IgH MRD clonotypes, were associated with relapse. In this analysis across two large transplant centers, we found that detection of MRD by NGS at a level of 10-6 offers significant prognostic value in adults with ALL undergoing HCT.

  View details for DOI 10.1182/bloodadvances.2023009856

  View details for PubMedID 37196642

• Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents. Blood Spinner, M. A., Sica, R. A., Tamaresis, J. S., Lu, Y., Chang, C., Lowsky, R., Frank, M. J., Johnston, L. J., Miklos, D. B., Muffly, L., Negrin, R. S., Rezvani, A. R., Shiraz, P., Shizuru, J. A., Weng, W. K., Binkley, M. S., Hoppe, R. T., Advani, R. H., Arai, S. 2023

  Abstract

  The treatment landscape of relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) has evolved significantly over the past decade following the approval of brentuximab vedotin (BV) and the programmed death-1 (PD-1) inhibitors. We evaluated how outcomes and practice patterns have changed for R/R cHL patients who underwent autologous hematopoietic cell transplantation (AHCT) at our institution from 2011-2020 (N=183) compared to 2001-2010 (N=159) and evaluated prognostic factors for progression-free survival (PFS) and overall survival (OS) in both eras. OS was superior in the modern era (4-year estimates 89.1% vs 79.0%, HR 0.53, 95% CI 0.33-0.85, p=0.011) with a trend towards lower non-relapse mortality beyond 2 years post-transplant. Among patients who progressed after AHCT, 4-year post-progression survival increased from 43.3% to 71.4% in the modern era, reflecting increasing use of BV and the PD-1 inhibitors. In multivariable analysis for patients transplanted in the modern era, age ³45 years, primary refractory disease, and lack of complete remission pre-AHCT were associated with inferior PFS, while receipt of a PD-1 inhibitor-based regimen pre-AHCT was associated with superior PFS (HR 0.21, 95% CI 0.05-0.80, p=0.030). Extranodal disease at relapse was associated with inferior OS (HR 3.12, 95% CI 1.25-7.77, p=0.014). Our study demonstrates improved survival for R/R cHL after AHCT in the modern era attributed to more effective salvage regimens allowing for better disease control pre-AHCT and improved outcomes for patients who progressed after AHCT. Excellent outcomes were observed with PD-1 inhibitor-based salvage regimens pre-AHCT and support a randomized trial evaluating immunotherapy in the second line setting.

  View details for DOI 10.1182/blood.2022018827

  View details for PubMedID 36857637

• Sequencing Antigen-Targeting Antibodies and Cellular Therapies in Adults With Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. American journal of hematology Aldoss, I., Shah, B. D., Park, J. H., Muffly, L., Logan, A. C., Brown, P., Stock, W., Jabbour, E. J. 2023

  Abstract

  The recent approvals of four CD19- or CD22-targeted therapies for B-cell acute lymphoblastic leukemia (B-ALL) have transformed the treatment of relapsed/refractory (r/r) disease. Adults with r/r B-ALL are usually eligible for all options, but there are no studies directly comparing these agents, and the treating physician must decide which to select. Each therapy has notable activity as a single agent but has limitations in particular settings, and the optimal choice varies. These therapies can be complementary and used either sequentially or concomitantly. Here, we review the current landscape of antigen-targeted therapies for r/r B-ALL and discuss considerations for their use. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ajh.26853

  View details for PubMedID 36691748

• Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy. The Neurohospitalist Satyanarayan, S., Spiegel, J., Hovsepian, D., Markert, M., Thomas, R., Muffly, L., Miklos, D., Graber, K., Scott, B. J. 2023; 13 (1): 53-60

  Abstract

  Immune Cell Effector Associated Neurotoxicity Syndrome (ICANS) is common amongst patients receiving CD19 targeted Chimeric Antigen Receptor T-cell (CAR-T) therapy. The purpose of this study is to characterize the incidence of seizures and ictal-interictal continuum (IIC) abnormalities in patients with ICANS.Retrospective review of consecutive patients treated with axicabtagene ciloleucel (axi-cel) for recurrent high-grade systemic lymphoma at Stanford Medical Center between 2/2016-6/2019. Electronic medical records (EMR) were reviewed for clinical features, treatment information, EEG data, CRS (cytokine release syndrome)/ICANS severity, and clinical outcomes.Fifty-six patients met inclusion criteria. 85.7% of patients developed CRS, and 58.9% developed ICANS. Twenty-eight patients had EEG monitoring, of whom 26 had ICANS. Median duration of EEG monitoring was 30 hours (range .5-126 hours). Four patients (7.1%) had seizures (1 patient had a clinical generalized seizure, 2 patients had clinical and nonconvulsive seizures, and 1 patient had an isolated non-convulsive seizure). Ictal-interictal continuum abnormalities were common, of which generalized periodic discharges (GPDs) with triphasic morphology and GPDs with epileptiform morphology were most frequently seen. Generalized periodic discharges with triphasic wave morphology were found across Grade 2-3 peak ICANS severity, however the majority (86%) of patients with epileptiform GPDs had Grade 3 peak ICANS severity.Among patients receiving axi-cel, seizure occurred in 7.1% of the total cohort, representing 12% of patients with ICANS. Ictal-interictal continuum abnormalities are also seen in patients with ICANS, most commonly GPDs. 75% of patients with seizures had nonconvulsive seizures supporting the use of continuous video EEG monitoring in this population.

  View details for DOI 10.1177/19418744221128852

  View details for PubMedID 36531846

  View details for PubMedCentralID PMC9755619

• Measurable residual disease in acute lymphoblastic leukemia: methods and clinical context in adult patients. Haematologica Saygin, C., Cannova, J., Stock, W., Muffly, L. 2022; 107 (12): 2783-2793

  Abstract

  Measurable residual disease (MRD) is the most powerful independent predictor of risk of relapse and long-term survival in adults and children with acute lymphoblastic leukemia (ALL). For almost all patients with ALL there is a reliable method to evaluate MRD, which can be done using multi-color flow cytometry, quantitative polymerase chain reaction to detect specific fusion transcripts or immunoglobulin/T-cell receptor gene rearrangements, and high-throughput next-generation sequencing. While next-generation sequencing-based MRD detection has been increasingly utilized in clinical practice due to its high sensitivity, the clinical significance of very low MRD levels (<10-4) is not fully characterized. Several new immunotherapy approaches including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T-cell therapies have demonstrated efficacy in eradicating MRD in patients with B-ALL. However, new approaches to target MRD in patients with T-ALL remain an unmet need. As our MRD detection assays become more sensitive and expanding novel therapeutics enter clinical development, the future of ALL therapy will increasingly utilize MRD as a criterion to either intensify or modify therapy to prevent relapse or de-escalate therapy to reduce treatment-related morbidity and mortality.

  View details for DOI 10.3324/haematol.2022.280638

  View details for PubMedID 36453516

• CD22 CAR T Cells Demonstrate Favorable Safety Profile and High Response Rates in Pediatric and Adult B-ALL: Results of a Phase 1b Study Jeyakumar, N., Ramakrishna, S., Frank, M. J., Sahaf, B., Feldman, S. A., Miklos, D. B., Mackall, C. L., Davis, K. L., Muffly, L., Schultz, L. M. AMER SOC HEMATOLOGY. 2022: 2374-2375

  View details for DOI 10.1182/blood-2022-164456

  View details for Web of Science ID 000893223202157

• Belumosudil Combination Therapy in Refractory Chronic Graft-Versus-Host Disease Chin, M., Shizuru, J. A., Muffly, L., Shiraz, P., Johnston, L. J., Lowsky, R., Rezvani, A. R., Frank, M. J., Bharadwaj, S., Weng, W., Negrin, R. S., Miklos, D. B., Arai, S. AMER SOC HEMATOLOGY. 2022: 4788-4789

  View details for DOI 10.1182/blood-2022-165547

  View details for Web of Science ID 000893223204356

• Outcomes for Acute Myeloid Leukemia Relapse after Allogeneic Hematopoietic Cell Transplantation Remain Poor in the Modern Era Philip, S., Lowsky, R., Johnston, L. J., Arai, S., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Bharadwaj, S., Frank, M. J., Miklos, D. B., Smith, M., Muffly, L., Agrawal, V. AMER SOC HEMATOLOGY. 2022: 4825-4827

  View details for DOI 10.1182/blood-2022-168546

  View details for Web of Science ID 000893223204372

• Comparison of Vital Status and Cause-Specific Mortality after Hematopoietic Cell Transplantation between the Center for International Blood and Marrow Transplant Research and the California Cancer Registry: A Record-Linkage Analysis from 1991 to 2018 Valcarcel, B., Schonfeld, S. J., Meyer, C. L., Brunson, A. M., Cooley, J. P., Abrahao, R., Wun, T., Auletta, J., Muffly, L., Keegan, T. M., Morton, L. M. AMER SOC HEMATOLOGY. 2022: 7684-7685

  View details for DOI 10.1182/blood-2022-160330

  View details for Web of Science ID 000893230300310

• Subsequent Solid Neoplasms Following Hematopoietic Cell Transplantation (HCT) for Hematologic Malignancies: Comparing Center for International Blood and Marrow Transplant Research (CIBMTR) and California Cancer Registry (CCR) Data Schonfeld, S. J., Valcarcel, B., Meyer, C. L., Brunson, A. M., Cooley, J. P., Abrahao, R., Wun, T., Auletta, J., Muffly, L., Keegan, T. M., Morton, L. M. AMER SOC HEMATOLOGY. 2022: 7670-7671

  View details for DOI 10.1182/blood-2022-159010

  View details for Web of Science ID 000893230300303

• Utilization of Autologous HCT in Multiple Myeloma: A Novel Linkage of CIBMTR, Cancer Registry and Hospitalization Data in California Esteghamat, N. S., Brunson, A. M., Wun, T., Rosenberg, A. S., Cooley, J. P., Schonfeld, S. J., Meyer, C. L., Valcarcel, B., Abrahao, R., Auletta, J., Morton, L. M., Muffly, L., Keegan, T. M. AMER SOC HEMATOLOGY. 2022: 10060-10062

  View details for DOI 10.1182/blood-2022-159776

  View details for Web of Science ID 000893230303032

• Real World Outcomes in Acute Myeloid Leukemia Patients Following Post Hematopoietic Stem-Cell Transplantation Maintenance Treatment with Midostaurin or Sorafenib: A US Retrospective Cohort Study Muffly, L., Young, C., Xie, B., Block, A., Touya, M., Pandya, B. J. AMER SOC HEMATOLOGY. 2022: 8111-8112

  View details for DOI 10.1182/blood-2022-157964

  View details for Web of Science ID 000893230301053

• Precision-Engineered Cell Therapy Orca-T Demonstrates High Relapse-Free Survival at 1 Year While Reducing Graft-Versus-Host Disease and Toxicity Oliai, C., Hoeg, R. T., Pavlova, A., Gandhi, A., Muffly, L., Mehta, R. S., Srour, S. A., Waller, E. K., Lowsky, R., Patel, S. S., Dholaria, B., Bachier, C., Pantin, J. M., Salhotra, A., McGuirk, J. P., Fernhoff, N. B., McClellan, J., Abedi, M., Negrin, R. S., Meyer, E. H. AMER SOC HEMATOLOGY. 2022

  View details for DOI 10.1182/blood-2022-165654

  View details for Web of Science ID 000893223200265

• Interim Update on the 'Watch' Registry, a Real-World Observational Study Using Clonoseq (R) to Monitor MRD in Lymphoid Malignancies Patel, K., Svoboda, J., Shah, B. D., Cheson, B. D., Azzi, G., Patel, K., Cowan, A. J., Muffly, L., Simmons, H., Schliekelman, M., Leonard, J. AMER SOC HEMATOLOGY. 2022: 5192-5194

  View details for DOI 10.1182/blood-2022-167669

  View details for Web of Science ID 000893223205097

• Geographical Barriers to Accessing Specialty Cancer Care Among Adolescents and Young Adults with Acute Lymphoblastic Leukemia Muffly, L., Garcia, A., Miller, K., Keegan, T. M., Parsons, H. AMER SOC HEMATOLOGY. 2022: 2402-2403

  View details for DOI 10.1182/blood-2022-163840

  View details for Web of Science ID 000893223202169

• Ultra-Sensitive Next-Generation Sequencing Establishes the Prognostic Value of Very Low MRD in Adults with Acute Lymphoblastic Leukemia Undergoing Hematopoietic Cell Transplantation Liang, E. C., Dekker, S. E., Sabile, J. G., Torelli, S., Zhang, A., Miller, K., Shiraz, P., Hayes-Lattin, B., Leonard, J., Muffly, L. AMER SOC HEMATOLOGY. 2022: 1732-1733

  View details for DOI 10.1182/blood-2022-157442

  View details for Web of Science ID 000893223201306

• Higher Rates of Severe Infection and Persistent Cytopenias in Long-Term CAR19 Responders Than after Autologous HCT: A Single Institution Study of 139 Subjects Hamilton, M. P., Liu-Fei, F. C., Alig, S. K., Tamaresis, J., Esfahani, M., Good, Z., Sworder, B., Schroers-Martin, J., Liu, C., Severinsen, F., Hanson, P. J., Lu, Y., Lowsky, R., Negrin, R. S., Meyer, E. H., Smith, M., Bharadwaj, S., Shizuru, J. A., Sidana, S., Shiraz, P., Rezvani, A. R., Johnston, L. J., Weng, W., Arai, S., Muffly, L., Dahiya, S., Diehn, M., Kurtz, D. M., Sahaf, B., Mackall, C. L., Frank, M. J., Miklos, D. B., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 7545-7547

  View details for DOI 10.1182/blood-2022-165600

  View details for Web of Science ID 000893230300247

• The Development of Carhlh after Axicabtagene Ciloleucel Is Associated with Poor Outcomes Philip, S., Srinagesh, H. K., Hamilton, M. P., Gentille, C., Mina, A., Arai, S., Johnston, L. J., Lowsky, R., Meyer, E. H., Negrin, R. S., Rezvani, A. R., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Bharadwaj, S., Dahiya, S., Muffly, L., Smith, M., Miklos, D. B., Frank, M. J. AMER SOC HEMATOLOGY. 2022: 12775-12777

  View details for DOI 10.1182/blood-2022-170877

  View details for Web of Science ID 000893230305401

• Analysis of Bendamustine Lymphodepletion, CD19 CART Expansion, Safety and Efficacy in Patients with Rel/Ref NonHodgkin Lymphoma Bharadwaj, S., Hamilton, M. P., Sahaf, B., Tamaresis, J., Patil, S., Hanson, P. J., Latchford, T., Arai, S., Johnston, L. J., Lowsky, R., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Meyer, E. H., Shiraz, P., Sidana, S., Smith, M., Weng, W., Muffly, L., Mackall, C. L., Frank, M. J., Miklos, D. B., Dahiya, S. AMER SOC HEMATOLOGY. 2022: 10371-10373

  View details for DOI 10.1182/blood-2022-170759

  View details for Web of Science ID 000893230303169

• Long-Term Follow-up of CD19/22 CAR Therapy in Children and Young Adults with B-ALL Reveals Efficacy, Tolerability and High Survival Rates When Coupled with Hematopoietic Stem Cell Transplantation Schultz, L. M., Ramakrishna, S., Baskar, R., Richards, R. M., Moon, J., Baggott, C., Fujimoto, M., Kunicki, M., Li, A., Jariwala, S., Erickson, C., Jacobs, A., Yamabe, K., Barsan, V., Majzner, R. G., Egeler, E. L., Mavroukakis, S., Ehlinger, Z., Reynolds, W. D., Sahaf, B., Muffly, L., Frank, M. J., Gramstrup, A., Chinnasamy, H., Patel, S., Miklos, D. B., Feldman, S. A., Mackall, C. L., Davis, K. L. AMER SOC HEMATOLOGY. 2022: 10300-10302

  View details for DOI 10.1182/blood-2022-167789

  View details for Web of Science ID 000893230303140

• Impact on caregivers and families of patients receiving chimeric antigen receptor T-cell therapy: a prospective longitudinal mixed methods study Litovich, C., Piehowski, C., Akinola, I., Crawford, E., D'Souza, A., Frank, M., Flynn, K., Knight, J., Lahijani, S., Miklos, D., Muffly, L., Sadana, S., Shah, N., Tan, I., Thiengmany, A., Cusatis, R. SPRINGER. 2022: S145

  View details for Web of Science ID 000922594700300

• Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy NEUROHOSPITALIST Satyanarayan, S., Spiegel, J., Hovsepian, D., Markert, M., Thomas, R., Muffly, L., Miklos, D., Graber, K., Scott, B. J. 2022

  View details for DOI 10.1177/19418744221128852

  View details for Web of Science ID 000867394200001

• CT-095 Disparities and Incomplete Capture of Race/Ethnicity Data in Adults With Hematologic Malignancies Referred for Cellular Therapies. Clinical lymphoma, myeloma & leukemia Molina, A., Muffly, L. 2022; 22 Suppl 2: S433-S434

  Abstract

  CONTEXT: Numerous reports demonstrate disparities in access to care, clinical trial enrollment, and survival outcomes in various hematologic malignancies based on race/ethnicity. Based on 2020 US Census data, the Stanford Cancer Institute catchment area includes a population of 32% Non-Hispanic White (NHW), 32% Hispanic, 25% Asian, and 5% Non-Hispanic Black (NHB).OBJECTIVE: To examine reporting of race/ethnicity and disparities in referral for, and receipt of, cellular therapies based on race/ethnicity in our region.METHODS: In this retrospective review of patient electronic medical records, we assessed race and ethnicity among adults referred to Stanford for hematopoietic cell transplantation (HCT) and chimeric antigen receptor T-cell (CAR-T) between 2018 and 2022. Race/ethnicity data were evaluated as was receipt of cellular therapy.RESULTS: For the 3,532 referred patients identified, 49% (N=1,743) were NHW compared to 17% (N=599) Hispanic, 15% (N=522) Asian and 5% (N=104) NHB patients; 19% (N=672) of referred patients had unknown race/ethnicity. Among those referred, 48% (N=1,695) actually received HCT and 9% (N=333) received CAR-T. The racial/ethnic distribution of HCT recipients were proportional to the referral population: 49% (N=836) NHW, 18% (N=312) Hispanic, 16% (N=273) Asian, 6% (N=95) NHB, and 25% (N=418) unknown, while CAR-T recipients were somewhat less likely to be NHB than the referral population: 54% (N=181) NHW, 17% (N=59) Hispanic, 13% (N=42) Asian, 3% (N=10) NHB, and 25% (N=82) unknown. Social determinants of health were not routinely captured among referred or treated patients.CONCLUSIONS: Approximately 20% of adult patients referred and receiving cellular therapies have unknown race/ethnicity. Referred patients did not match our catchment area, with Hispanic patients comprising 50% fewer referrals than anticipated. The race/ethnicity of patients treated was overall consistent with the distribution of patients referred, suggesting that disparities are occurring more at the referral level. These data have prompted an interventional project aimed at better capturing race/ethnicity and social determinants of health among all adults referred for HCT and CAR-T cell therapy at Stanford.

  View details for DOI 10.1016/S2152-2650(22)01645-7

  View details for PubMedID 36164197

• Disparities and Incomplete Capture of Race/Ethnicity Data in Adults With Hematologic Malignancies Referred for Cellular Therapies Molina, A., Muffly, L. CIG MEDIA GROUP, LP. 2022: S433-S434

  View details for Web of Science ID 000897948100524

• Linking the Center for International Blood and Marrow Transplant Research (CIBMTR) Registry to the California Cancer Registry and California Hospital Patient Discharge Data. Transplantation and cellular therapy Keegan, T. H., Brunson, A., Cooley, J. J., Schonfeld, S. J., Meyer, C. L., Valcarcel, B., Abrahao, R., Wun, T., Auletta, J., Muffly, L., Morton, L. M. 2022

  Abstract

  Advances in hematopoietic cell transplant (HCT) have substantially improved patient survival, increasing the importance of studying outcomes and long-term adverse effects in the rapidly growing population of HCT survivors. Large-scale registry data from the Center for International Blood and Marrow Transplant Research (CIBMTR) are a valuable resource for studying mortality and late effects after HCT, with detailed data reported by HCT centers on transplant-related factors and key outcomes.To evaluate the robustness of CIBMTR outcome data and to assess health-related outcomes and healthcare utilization among HCT recipients, we linked data from the CIBMTR for California residents with the population-based California Cancer Registry (CCR) and hospitalization information from the California Patient Discharge Database (PDD).In this retrospective cohort study, probabilistic and deterministic record linkage utilized key patient identifiers, such as social security number, zip code, sex, birth date, hematologic malignancy type and diagnosis date, and HCT type and date.Among 22,733 patients in the CIBMTR who received autologous or allogeneic HCT for hematologic malignancy during 1991-2016, 89.0% were matched to the CCR and/or PDD (N=17,707 [77.9%] both; N=1179 [5.2%] CCR only; N=1342 [5.9%] PDD only). Unmatched patients were slightly more likely to have a first autologous (12.6%) than allogeneic (9.0%) HCT, a higher number of missing linkage identifiers, and to have received their HCT occurring prior to 2010. Among the patients reported to CIBMTR who matched to CCR, 85.7% demonstrated concordance of both hematologic malignancy type and diagnosis date across data sources.This linkage presents unparalleled opportunities to advance understanding of HCT practices and patient outcomes.

  View details for DOI 10.1016/j.jtct.2022.09.016

  View details for PubMedID 36174935

• Post-infusion CAR T-Reg cells identify patients resistant to CD19-CAR therapy NATURE MEDICINE Good, Z., Spiegel, J. Y., Sahaf, B., Malipatlolla, M. B., Ehlinger, Z. J., Kurra, S., Desai, M. H., Reynolds, W. D., Lin, A., Vandris, P., Wu, F., Prabhu, S., Hamilton, M. P., Tamaresis, J. S., Hanson, P. J., Patel, S., Feldman, S. A., Frank, M. J., Baird, J. H., Muffly, L., Claire, G. K., Craig, J., Kong, K. A., Wagh, D., Coller, J., Bendall, S. C., Tibshirani, R. J., Plevritis, S. K., Miklos, D. B., Mackall, C. L. 2022

  Abstract

  Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4+Helios+ CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity. Deep profiling demonstrated that this population is non-clonal and manifests hallmark features of T regulatory (TReg) cells. Validation cohort analysis upheld the link between higher CAR TReg cells with clinical progression and less severe neurotoxicity. A model combining expansion of this subset with lactate dehydrogenase levels, as a surrogate for tumor burden, was superior for predicting durable clinical response compared to models relying on each feature alone. These data credential CAR TReg cell expansion as a novel biomarker of response and toxicity after CAR T cell therapy and raise the prospect that this subset may regulate CAR T cell responses in humans.

  View details for DOI 10.1038/s41591-022-01960-7

  View details for Web of Science ID 000852940800007

  View details for PubMedID 36097223

• Treatment-related toxicities associated with hospitalization in children, adolescents, and young adults with acute lymphoblastic leukemia: population level analysis. Leukemia & lymphoma Namjoshi, N. S., Keegan, T. H., Li, Q. C., Chung, J. H., Rosenthal, J. L., Winestone, L. E., Muffly, L., Malogolowkin, M. H., Alvarez, E. M. 2022: 1-9

  Abstract

  Treatment-related toxicities (TRTs) are a potential cause of survival disparities in patients with acute lymphoblastic leukemia (ALL). We aimed to identify the most frequent TRTs associated with hospitalizations at a population level in children, adolescents and young adults (AYAs). We used the California Cancer Registry linked to a statewide hospital discharge database to identify children and AYAs with TRTs within 3 years of diagnosis. We assessed the frequency of TRTs, length of stay (LOS), admission rates associated with TRTs and TRTs impact on survival. Febrile neutropenia, hypertension, and thrombocytopenia were the most common TRTs for both children and AYAs. AYAs had longer median LOS compared to children for most toxicities. AYAs at non-specialized cancer centers (SCCs) had higher frequency of admissions associated with TRTs compared to non-SCC. Cardiovascular, respiratory, gastrointestinal, renal, and infectious TRTs were associated with worse survival. This study demonstrates the burden of TRTs in patients with ALL.

  View details for DOI 10.1080/10428194.2022.2113533

  View details for PubMedID 35999808

• SOHO State of the Art Updates and Next Questions: Measurable Residual Disease in Acute Lymphoblastic Leukemia - Optimization and Innovation in 2022 and Beyond. Clinical lymphoma, myeloma & leukemia Dekker, S. E., Leonard, J., Muffly, L. 2022

  Abstract

  Measurable residual disease (MRD) is an established component of acute lymphoblastic leukemia (ALL) management in both children and adults. Society guidelines and expert consensus documents include assessment of MRD as the standard of care following induction therapy, consolidation therapy, and at additional time points, depending on the treatment regimen administered. Further, the approval of blinatumomab for MRD+ B-ALL has advanced the concept of MRD response as a clinical endpoint in ALL. Although the utility of MRD in ALL has been well defined over the last decades, several questions remain. In this review we focus on areas of ongoing controversy and exploration in ALL MRD, including the following: (1) Does increasing the depth of MRD assessment add prognostic value? (2) Is there a role for ongoing MRD monitoring once patients achieve MRD response? (3) Can MRD assessment of the peripheral blood be substituted for bone marrow? (4) Should MRD assays be applied to the analysis of the central nervous system (CNS)? Ongoing studies should answer the majority of these questions in the coming years.

  View details for DOI 10.1016/j.clml.2022.08.004

  View details for PubMedID 36130863

• Disparities in trial enrollment and outcomes of Hispanic adolescent and young adult acute lymphoblastic leukemia. Blood advances Muffly, L., Yin, J., Jacobson, S., Wall, A., Quiroz, E., Advani, A. S., Luger, S. M., Tallman, M. S., Litzow, M. R., Foster, M. C., Erba, H. P., Appelbaum, F. R., Larson, R. A., Keegan, T. H., Stock, W. 2022; 6 (14): 4085-4092

  Abstract

  In this secondary analysis of Hispanic adolescents and young adults (AYA) with acute lymphoblastic leukemia (ALL) treated on Cancer and Leukemia Group B (CALGB) 10403, we evaluated outcomes and geographic enrollment patterns relative to US population data. We used demographic, clinical, and survival data on AYAs enrolled on CALGB 10403 (N = 295, 2007-2012). Surveillance, Epidemiology, and End Results registries provided overall survival (OS) for US AYA ALL by ethnicity/race. North American Association of Cancer Registries provided AYA ALL incidence overall and proportion among Hispanics by US state. Of AYAs enrolled on CALGB 10403, 263 (89%) reported ethnicity/race: 45 (17%) Hispanic, 172 (65%) non-Hispanic White (NHW), 25 (10%) non-Hispanic Black (NHB), and 21 (8%) other. Compared with NHWs, Hispanic and NHB patients had lower household income, and Hispanic patients were more likely to harbor high-risk CRLF2 aberrations. Relative to US estimates, where Hispanic patients represented 46% of newly diagnosed AYA ALL patients and experienced inferior OS compared with NHW (P < .001), Hispanic AYAs on CALGB 10403 did as well as NHW patients (3 year OS, 75% vs 74%; P = NS). Hispanic patients also had higher rates of protocol completion (P = .05). Enrollments on CALGB 10403 differed relative to the distribution of Hispanic AYA ALL in the United States: enrollment was highest in the Midwest; t and only 15% of enrollees were from states with a high proportion of Hispanic AYA ALL patients. In summary, Hispanic patients treated on CALGB 10403 did as well as NHWs and better than population estimates. Geographical misalignment between trial sites and disease epidemiology may partially explain the lower-than-expected enrollment of Hispanic AYA ALL patients.

  View details for DOI 10.1182/bloodadvances.2022007197

  View details for PubMedID 35838753

• Disparities in trial enrollment and outcomes of Hispanic adolescent and young adult acute lymphoblastic leukemia BLOOD ADVANCES Muffly, L., Yin, J., Jacobson, S., Wall, A., Quiroz, E., Advani, A. S., Luger, S. M., Tallman, M. S., Litzow, M. R., Foster, M. C., Erba, H. P., Appelbaum, F. R., Larson, R. A., Keegan, T. M., Stock, W. 2022; 6 (14): 4085-4092

  View details for DOI 10.1182/bloodadvances.2022007197.

  View details for Web of Science ID 000855338300001

• Measurable residual disease in acute lymphoblastic leukemia: techniques and therapeutic utility. Clinical advances in hematology & oncology : H&O Muffly, L. 2022; 20 (7): 419-421

  View details for PubMedID 35802871

• Measurable Residual Disease in Acute Lymphoblastic Leukemia: Techniques and Therapeutic Utility CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY Muffly, L. 2022; 20 (7): 419-421

  View details for Web of Science ID 000822648800002

• Reverse fate mapping of CD19-targeted CAR T cells in patients with large B-cell lymphoma Good, Z., Hamilton, M. P., Spiegel, J. Y., Kurra, S., Desai, M., Prabhu, S., Yang, E., Ozawa, M. G., Hanson, P. J., Wu, F., Frank, M. J., Baird, J. H., Muffly, L., Claire, G. K., Craig, J., Kong, K. A., Wagh, D., Coller, J., Plevritis, S. K., Sahaf, B., Miklos, D. B., Mackall, C. L. AMER ASSOC CANCER RESEARCH. 2022

  View details for Web of Science ID 000892509507391

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia in the Modern Era. Transplantation and cellular therapy Liang, E. C., Craig, J., Torelli, S., Cunanan, K., Iglesias, M., Arai, S., Frank, M. J., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R., Rezvani, A., Shiraz, P., Shizuru, J., Sidana, S., Weng, W. K., Bharadwaj, S., Muffly, L. 2022

  Abstract

  Allogeneic hematopoietic cell transplantation (HCT) remains an important treatment for adults with acute lymphoblastic leukemia (ALL). We hypothesized that advances in ALL and transplantation have resulted in improved HCT outcomes in recent years.To evaluate the characteristics and outcomes of adult ALL patients undergoing allogeneic HCT over the last decade.Patients with ALL aged ≥18 years old who underwent allogeneic HCT at Stanford University between 2008 and 2019 were included in this study. Patients were divided into two Eras based on year of HCT: 2008-2013 (Earlier Era) and 2014-2019 (Later Era).A total of 285 patients were included: 119 patients underwent HCT in the Earlier Era and 166 in the Later Era. Patients transplanted in the Later Era were more likely to be Hispanic (38% vs. 21%) and to have HCT-Comorbidity Index of ≥ 3 (31% vs. 18%). Donor source for HCT also differed with an increase in the use of HLA-mismatched donor sources (38% vs. 24%), notably umbilical cord blood (UCB) in the Later Era (16% vs. 0%). Patients in the Later Era were less likely to undergo transplant with active disease (4% vs.16%); pre-HCT rates of measurable residual disease (MRD) were similar across the Eras (38% vs. 40%). In unadjusted analyses, overall survival (OS) improved across Eras, with 2-year estimates for the Later and Earlier Eras of 73% (95% CI, 66%-80%) vs. 55% (95% CI, 46%-64%), respectively. Multivariable analysis confirmed the association between Later Era and OS (HR = 0.52, 95% CI, 0.34-0.78). Finally, among patients relapsing after HCT (25% in Later Era and 33% in Earlier Era), the utilization of novel immunotherapies increased in the Later Era (44% vs. 3%), as did the median OS following post-HCT relapse (16 months vs. 8 months, p < 0.001).OS following HCT for adult ALL has improved in recent years. This is due, in part, to a significant improvement in the ability to effectively salvage adults with ALL relapsing after HCT.

  View details for DOI 10.1016/j.jtct.2022.05.010

  View details for PubMedID 35584783

• Innovative Approaches to the Management of Acute Lymphoblastic Leukemia Across the Age Spectrum. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Curran, E., Muffly, L., Luskin, M. R. 2022; 42: 1-11

  Abstract

  Adults compose nearly half of all patients diagnosed with acute lymphoblastic leukemia (ALL) and historically have had poor survival compared with pediatric patients. Recently approved therapies, such as monoclonal antibodies, CAR T-cell constructs, and next-generation tyrosine kinase inhibitors, have improved survival in relapsed and refractory ALL, and studies are now examining incorporating these treatments and others into the upfront setting. In adolescent and young adult patients, use of pediatric-based regimens has already improved survival compared with historical controls, and the addition of monoclonal antibodies, such as inotuzumab ozogamicin and blinatumomab, may further enhance this survival benefit. In older adults, approaches have centered on minimizing conventional chemotherapy to decrease toxicity by incorporating monoclonal antibodies and other novel therapies to increase efficacy. With the addition of tyrosine kinase inhibitors to chemotherapy for patients with Philadelphia chromosome-positive ALL, survival of this once poor-prognosis ALL subtype now approaches or exceeds outcomes of other subtypes of adult ALL. Further refinements in the backbone treatment regimen and optimal consolidation approaches will likely improve survival further. Although allogeneic hematopoietic stem cell transplant was previously routinely used as consolidation for adults with ALL, incorporation of measurable residual disease and other risk stratification strategies has enabled better identification of patients who will benefit from allogeneic hematopoietic stem cell transplant. Ongoing clinical trials investigating these approaches will continue the evolution of treatment approaches for adults with ALL, with further improvement in outcomes anticipated.

  View details for DOI 10.1200/EDBK_349647

  View details for PubMedID 35503981

• Controversies in the Treatment of Adolescents and Young Adults with Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. Current oncology reports Grover, P., Muffly, L. 2022

  Abstract

  PURPOSE OF THE REVIEW: The incidence of acute lymphoblastic leukemia (ALL) has been increasing steadily in the adolescent and young adult (AYA) population. In this review article focused on the management of AYAs with Philadelphia chromosome-negative (Ph-) B-ALL, we examine topics of clinical interest and identify areas of controversy in need of further investigation.RECENT FINDINGS: We explore four areas of active investigation: pediatric-inspired front-line treatment regimens, the optimal time of measurable residual disease (MRD) assessment, the role of hematopoietic stem cell transplant and the optimal salvage therapy for relapsed/refractory B-ALL in AYAs. There has been rapid advancement in the management of ALL in the AYA patient population, which has resulted in improved outcomes. We must build on the successes by continuing to promote multi-center innovative clinical research with clinical trial populations reflecting the AYA ALL patient spectrum. The incorporation of novel targeted immunotherapy into front-line treatment will be transformative and redefine treatment paradigms in the coming years.

  View details for DOI 10.1007/s11912-022-01276-2

  View details for PubMedID 35353349

• Real-world Experience of Cryopreserved Allogeneic Hematopoietic Grafts in the COVID-19 Pandemic: A Single Center Report. Transplantation and cellular therapy Bankova, A. K., Caveney, J., Yao, B., Ramos, T. L., Bogeholz, J., Heydari, K., Diaz, N., Jackson, M. L., Lowsky, R., Brown, J. W., Johnston, L., Rezvani, A. R., Frank, M. J., Muffly, L., Weng, W., Sidana, S., Negrin, R. S., Miklos, D. B., Shiraz, P., Meyer, E. H., Shizuru, J. A., Arai, S. 1800

  Abstract

  BACKGROUND: As a result of the COVID-19 widespread pandemic, cryopreservation of allogeneic donor apheresis products was implemented to mitigate the challenges of donor availability and product transport. Although logistically beneficial, the impact of cryopreservation on clinical outcomes and graft composition remains unclear.OBJECTIVES: To compare the outcomes and graft composition with cryopreserved versus fresh allografts in the setting of allogeneic hematopoietic cell transplantation (allo-HCT).STUDY DESIGN: We retrospectively analyzed the clinical outcomes of 30 consecutive patients who received cryopreserved allografts between March and August 2020 as compared to 60 consecutive patients who received fresh allografts prior to the COVID-19 pandemic. Primary endpoints were hematopoietic engraftment, graft failure (GF) and secondary outcomes were overall survival (OS), relapse free survival (RFS) and non-relapse mortality (NRM). In addition, extended immunophenotype analysis was performed on cryopreserved versus prospectively collected fresh apheresis samples.RESULTS: Compared to fresh allografts, both neutrophil and platelet recovery were delayed in recipients of cryopreserved reduced intensity conditioning (RIC) allo-HCT with median times to engraftment of 24 days vs 18 days (P = .01) and 27 days vs 18 days (P = .069), respectively. We observed primary GF in 4 of 30 patients in the cryopreserved cohort (13.3%) vs only one of 60 patients (1.7 %) in the fresh cohort (P = .03). Cryopreserved RIC allo-HCT was associated with significantly lower median total, myeloid and T-cell donor chimerism at 1 month. OS and RFS were inferior for cryograft recipients with hazard ratio [HR (95%Cl)]: 2.16 (1.00, 4.67) and 1.90 (0.95, 3.79), respectively. Using an extended immunophenotype analysis we compared 14 samples from the cryopreserved cohort to 6 prospectively collected fresh apheresis donor samples. These analyses showed both decrease in total cell viability and significantly reduced absolute numbers of NK cells (CD3-CD56+) in the cryopreserved apheresis samples.CONCLUSION: In this single institution study we note delayed engraftment and a trend toward clinical inferiority of cryopreserved vs fresh allografts. Further evaluation of the use of cryopreserved allografts and their impact on clinical and laboratory outcomes is warranted.

  View details for DOI 10.1016/j.jtct.2022.01.010

  View details for PubMedID 35042013

• Correction to: Measurable residual disease status and FLT3 inhibitor therapy in patients with FLT3-ITD mutated AML following allogeneic hematopoietic cell transplantation. Bone marrow transplantation Liang, E. C., Chen, C., Lu, R., Mannis, G. N., Muffly, L. 2022

  View details for DOI 10.1038/s41409-022-01606-9

  View details for PubMedID 35169285

• Outcomes of Allogeneic Transplantation after Hypomethylating Agents with Venetoclax in Acute Myeloid Leukemia. American journal of hematology Kennedy, V. E., Hui, G., Azenkot, T., Gaut, D., Wieduwilt, M. J., Oliai, C., Jonas, B. A., Mittal, V., Logan, A. C., Muffly, L. S., Mannis, G. N. 2022

  View details for DOI 10.1002/ajh.26524

  View details for PubMedID 35266185

• Randomized Phase III BMT CTN Trial of Calcineurin Inhibitor-Free Chronic Graft-Versus-Host Disease Interventions in Myeloablative Hematopoietic Cell Transplantation for Hematologic Malignancies. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Luznik, L., Pasquini, M. C., Logan, B., Soiffer, R. J., Wu, J., Devine, S. M., Geller, N., Giralt, S., Heslop, H. E., Horowitz, M. M., Jones, R. J., Litzow, M. R., Mendizabal, A., Muffly, L., Nemecek, E. R., O'Donnell, L., O'Reilly, R. J., Palencia, R., Schetelig, J., Shune, L., Solomon, S. R., Vasu, S., Ho, V. T., Perales, M. 2021: JCO2102293

  Abstract

  PURPOSE: Calcineurin inhibitors (CNI) are standard components of graft-versus-host disease (GVHD) prophylaxis after hematopoietic cell transplantation (HCT). Prior data suggested that CNI-free approaches using donor T-cell depletion, either by ex vivo CD34 selection or in vivo post-transplant cyclophosphamide (PTCy) as a single agent, are associated with lower rates of chronic GVHD (cGVHD).METHODS: This multicenter phase III trial randomly assigned patients with acute leukemia or myelodysplasia and an HLA-matched donor to receive CD34-selected peripheral blood stem cell, PTCy after a bone marrow (BM) graft, or tacrolimus and methotrexate after BM graft (control). The primary end point was cGVHD (moderate or severe) or relapse-free survival (CRFS).RESULTS: Among 346 patients enrolled, 327 received HCT, 300 per protocol. Intent-to-treat rates of 2-year CRFS were 50.6% for CD34 selection (hazard ratio [HR] compared with control, 0.80; 95% CI, 0.56 to 1.15; P = .24), 48.1% for PTCy (HR, 0.86; 0.61 to 1.23; P = .41), and 41.0% for control. Corresponding rates of overall survival were 60.1% (HR, 1.74; 1.09 to 2.80; P = .02), 76.2% (HR, 1.02; 0.60 to 1.72; P = .95), and 76.1%. CD34 selection was associated with lower moderate to severe cGVHD (HR, 0.25; 0.12 to 0.52; P = .02) but higher transplant-related mortality (HR, 2.76; 1.26 to 6.06; P = .01). PTCy was associated with comparable cGVHD and survival outcomes to control, and a trend toward lower disease relapse (HR, 0.52; 0.28 to 0.96; P = .037).CONCLUSION: CNI-free interventions as performed herein did not result in superior CRFS compared with tacrolimus and methotrexate with BM. Lower rates of moderate and severe cGVHD did not translate into improved survival.

  View details for DOI 10.1200/JCO.21.02293

  View details for PubMedID 34855460

• Mgta-145+Plerixafor Provides GCSFFree Rapid and Reliable Hematopoietic Stem Cell Mobilization for Autologous Stem Cell Transplant in Patients with Multiple Myeloma: A Phase 2 Study Sidana, S., Bankova, A. K., Hosoya, H., Kumar, S., Tamaresis, J., Le, A., Muffly, L., Johnston, L. J., Arai, S., Lowsky, R., Meyer, E. H., Rezvani, A. R., Weng, W., Frank, M. J., Shiraz, P., Girgenti, D., Goncalves, K. A., Schmelmer, V., Davis, J. C., Lu, Y., Shizuru, J. A., Miklos, D. B. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-149306

  View details for Web of Science ID 000736413908010

• Enrollment Characteristics and Outcomes of Hispanic and Black AYA ALL Patients Enrolled on a US Intergroup Clinical Trial: A Comparison of the CALGB 10403 (Alliance) Cohort with US Population-Level Data Muffly, L., Yin, J., Jacobson, S., Advani, A., Luger, S. M., Tallman, M. S., Litzow, M. R., Foster, M. C., Appelbaum, F. R., Larson, R. A., Keegan, T., Stock, W. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-148804

  View details for Web of Science ID 000736398801114

• First Salvage Therapy for Relapsed or Refractory Acute Myeloid Leukemia: Associated Health Care Resource Use and Costs Muffly, L., Young, C., Nimke, D., Sullivan, L., Feng, Q., Pandya, B. J. AMER SOC HEMATOLOGY. 2021: 1936-+

  View details for DOI 10.1182/blood-2021-145397

  View details for Web of Science ID 000736398807173

• Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study Cusatis, R., Tan, I., Piehowski, C., Akinola, I., Crawford, E., Craig, J., Thiengmany, A., Frank, M. J., Miklos, D. B., Shah, N. N., D'Souza, A., Knight, J. M., Muffly, L., Flynn, K. E., Sidana, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-146032

  View details for Web of Science ID 000736398802108

• Do PROs Tell the Whole Story? Differential Outcomes Based on PatientReported Outcomes (PROs) Versus Performance-Based Metrics (PBM) on Cognition for Patients Receiving Chimeric Antigen Receptor (CAR)-T Cell Therapy Tan, I., Cusatis, R., Crawford, E., Thiengmany, A., Piehowski, C., Akinola, I., Craig, J., Lahijani, S., Frank, M. J., Shah, N. N., D'Souza, A., Miklos, D. B., Muffly, L., Flynn, K. E., Sidana, S. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-145746

  View details for Web of Science ID 000736413904116

• Outcomes for Myelofibrosis Patients Following Myeloablative Allogeneic Stem Cell Transplantation Using the Orca-T Graft from HLA-Matched Related and Unrelated Donors Arpita, G., Moroz, A., Muffly, L., Shiraz, P., Schachter, L., Fernhoff, N. B., McClellan, J., Negrin, R. S., Gotlib, J., Meyer, E. H. AMER SOC HEMATOLOGY. 2021: 1819-+

  View details for DOI 10.1182/blood-2021-150521

  View details for Web of Science ID 000736398807057

• Measurable Residual Disease Status and FLT3 Inhibitor Therapy in Patients with FLT3-ITD Mutated AML Following Allogeneic Hematopoietic Cell Transplantation Liang, E. C., Chen, C., Lu, R., Mannis, G. N., Muffly, L. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-149805

  View details for Web of Science ID 000736398805037

• Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy BLOOD ADVANCES Johnsrud, A., Craig, J., Baird, J., Spiegel, J., Muffly, L., Zehnder, J., Tamaresis, J., Negrin, R., Johnston, L., Arai, S., Shizuru, J., Lowsky, R., Meyer, E., Weng, W., Shiraz, P., Rezvani, A., Latchford, T., Mackall, C., Miklos, D., Frank, M., Sidana, S. 2021; 5 (21): 4465-4475

  View details for DOI 10.1182/bloodadvances.2021004716.

  View details for Web of Science ID 000718993700016

• Historical perspective and a glance into the antibody-based conditioning regimens: A new era in the horizon? Blood reviews El Fakih, R., Lazarus, H. M., Muffly, L., Altareb, M., Aljurf, M., Hashmi, S. K. 2021: 100892

  Abstract

  The hematopoietic cell transplantation practice has changed significantly over the years. More than 1500 centers around the globe are offering transplant for different types of diseases. This growth was driven by improving the efficacy and the safety of the procedure and the ability to use alternate donors. These improvements made the procedure feasible in virtually all patients in need for it. With the availability of novel therapies and targeted agents, we may be witnessing a new transplant-era. These agents may help to circumvent some of the remaining limitations of the procedure and open the doors for new indications. Herein, we review historical transplant milestones, the accomplishments that led to the modern transplant practice and we discuss the idea of minimal-intensity conditioning and the possibility to adopt chemotherapy and radiation-free preparative regimens in the near future.

  View details for DOI 10.1016/j.blre.2021.100892

  View details for PubMedID 34674852

• Chimeric Antigen Receptor-T Cell Therapy in Adults with B-Cell Acute Lymphoblastic Leukemia: A Systematic Review. Blood advances Grover, P., Veilleux, O., Tian, L., Sun, R., Previtera, M., Curran, E., Muffly, L. 2021

  Abstract

  Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase and Cochrane Library for prospective, interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥ 18 years. Risk of bias was assessed using a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean CR rate was 81% and MRD negative remission rate was 81% at 4 weeks post CAR-T infusion. With median follow-up across studies of 24 months the cumulative 12-month probability of PFS and OS were 37% (95% CI 26-48%) and 57% (95% CI 49-65%), respectively. Relapse occurred in 40.3%; target antigen was retained in 73.2% of relapses. Across studies, any grade of CRS occurred in 82% (95% CI 61-95%) and grade 3 or higher CRS in 27% (95% CI 18-36%). Neurotoxicity of any grade occurred in 34% (95% CI 24-47%) and grade 3 or higher in 14% (95% CI 1-25%). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.

  View details for DOI 10.1182/bloodadvances.2020003482

  View details for PubMedID 34610109

• Haploidentical vs. sibling, unrelated, or cord blood hematopoietic cell transplantation for acute lymphoblastic leukemia. Blood advances Wieduwilt, M. J., Metheny, L., Zhang, M., Wang, H., Estrada-Merly, N., Marks, D. I., Al-Homsi, A. S., Muffly, L., Chao, N. J., Rizzieri, D., Gale, R. P., Gadalla, S. M., Cairo, M. S., Mussetti, A., Gore, S. D., Bhatt, V. R., Patel, S. S., Michelis, F. V., Inamoto, Y., Badawy, S. M., Copelan, E., Palmisiano, N., Kharfan-Dabaja, M. A., Lazarus, H. M., Ganguly, S., Bredeson, C. N., Diaz Perez, M. A., Cassaday, R., Savani, B. N., Ballen, K. K., Martino, R., Wirk, B., Bacher, U., Aljurf, M., Bashey, A., Murthy, H. S., Yared, J. A., Aldoss, I., Farhadfar, N., Liu, H., Abdel-Azim, H., Waller, E. K., Solh, M., Seftel, M., van der Poel, M. W., Grunwald, M. R., Liesveld, J. L., Kamble, R. T., McGuirk, J. P., Munker, R., Cahn, J., Lee, J. W., Freytes, C. O., Krem, M., Winestone, L. E., Gergis, U., Nathan, S., Olsson, R. F., Verdonck, L. F., Sharma, A., Ringden, O., Friend, B. D., Cerny, J., Choe, H. K., Chhabra, S., Nishihori, T., Seo, S., George, B., Baxter-Lowe, L. A., Hildebrandt, G. C., de Lima, M., Litzow, M. R., Kebriaei, P., Hourigan, C. S., Abid, M. B., Weisdorf, D. J., Saber, W. 2021

  Abstract

  The role of haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PTCy) for acute lymphoblastic leukemia (ALL) is being defined. We performed a retrospective, multivariate analysis comparing outcomes of HCT approaches by donor for adults with ALL in remission. The primary objective was to compare overall survival (OS) between haploidentical HCT using PTCy and HLA-matched sibling donor (MSD), 8/8 HLA-matched unrelated donor (MUD) , 7/8 HLA-matched UD, or umbilical cord blood (UCB) HCT. Comparing haploidentical to MSD HCT, OS, leukemia-free survival (LFS), non-relapse mortality (NRM), relapse, and acute graft-versus-host disease (aGVHD) were not different but chronic GVHD (cGVHD) was higher with MSD HCT. Compared to MUD HCT, OS, LFS, and relapse were not different but MUD HCT had increased NRM (HR 1.42, P=0.02), grade 3-4 aGVHD (HR 1.59, P=0.005), and cGVHD. Compared to 7/8 UD HCT, LFS and relapse were not different, but 7/8 UD HCT had worse OS (HR 1.38, P=0.01) and increased NRM (HR 2.13, P=<0.001), grade 3-4 aGVHD (HR 1.86, P=0.003), and cGVHD (HR 1.72, P=<0.001). Compared to UCB HCT, late OS , late LFS, relapse, and cGVHD were not different but UCB HCT had worse early OS (≤18 months, HR 1.93, P<0.001), worse early LFS (HR 1.40, P=0.007) and increased incidences of NRM (HR 2.08, P<0.001) and grade 3-4 aGVHD (HR 1.97, P<0.001). Haploidentical HCT using PTCy showed no difference in survival but less GVHD compared to traditional MSD and MUD HCT and is the preferred alternative donor HCT option for adults with ALL in CR.

  View details for DOI 10.1182/bloodadvances.2021004916

  View details for PubMedID 34547770

• Chimeric Antigen Receptor T-Cell Therapy (CAR-T) in Adults with B-Cell Acute Lymphoblastic Leukemia (B-ALL): A Systematic Review and Meta-Analysis Grover, P., Veilleux, O., Tian, L., Sun, R., Previtera, M., Curran, E., Muffly, L. CIG MEDIA GROUP, LP. 2021: S454

  View details for Web of Science ID 000691910500446

• Measurable Residual Disease in Acute Lymphoblastic Leukemia: Optimization and Innovation in 2021 and Beyond Muffly, L. CIG MEDIA GROUP, LP. 2021: S85-S87

  View details for Web of Science ID 000691910500034

• Measurable Residual Disease Status and FLT3 Inhibitor Therapy in Patients with FLT3-ITD-Mutated AML Following Allogeneic Hematopoietic Cell Transplantation Liang, E. C., Chen, C., Lu, R., Mannis, G. N., Muffly, L. CIG MEDIA GROUP, LP. 2021: S278-S279

  View details for Web of Science ID 000691910500112

• Frontline treatment patterns and outcomes among older adults with acute myeloid leukemia: A population-based analysis in the modern era. Cancer Kennedy, V. E., Keegan, T. H., Li, Q., Maguire, F. B., Muffly, L. S. 2021

  Abstract

  BACKGROUND: Traditionally, conventional induction chemotherapy has been the primary frontline treatment for acute myeloid leukemia (AML); however, older adults are often poor chemotherapy candidates. Recently, several nonconventional frontline AML regimens, including hypomethylating agents, the BCL-2 inhibitor venetoclax, and targeted therapies, have emerged, and they may offer new options for older adults. This study was aimed at describing treatment patterns and outcomes of older adult AML in a modern population-based cohort.METHODS: This study evaluated patients aged ≥60 years with a first primary diagnosis of AML (2014-2017) in the California Cancer Registry linked to inpatient hospitalizations. Multivariable regression examined factors associated with the frontline treatment regimen and survival.RESULTS: In all, 3068 patients were included; 36% received frontline therapy with a conventional chemotherapy backbone, 42% received nonconventional therapy, and 22% received no treatment. The use of nonconventional therapy increased over time from 38% of patients in 2014 to 47% in 2017 (P < .001). In multivariable analyses, receipt of treatment was associated with an age younger than 80 years, fewer than 2 comorbidities, and care at a National Cancer Institute-designated cancer center (NCI-CC). Compared with conventional chemotherapy, nonconventional therapy was associated with Black race/ethnicity, public health insurance, fewer hospital admissions, and fewer inpatient days. Receiving frontline therapy at an NCI-CC was independently associated with superior overall survival.CONCLUSIONS: Using a population-based approach, this study has demonstrated that patterns of care for frontline AML treatment in older adults are changing, with increasing use of nonconventional therapies. A significant proportion of older adults remain untreated. At the population level, there remain opportunities to increase therapy access for older adults with AML.

  View details for DOI 10.1002/cncr.33873

  View details for PubMedID 34436782

• Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research. Haematologica Lazaryan, A., Dolan, M., Zhang, M., Wang, H., Kharfan-Dabaja, M. A., Marks, D. I., Bejanyan, N., Copelan, E., Majhail, N. S., Waller, E. K., Chao, N., Prestidge, T., Nishihori, T., Kebriaei, P., Inamoto, Y., Hamilton, B., Hashmi, S. K., Kamble, R. T., Bacher, U., Hildebrandt, G. C., Stiff, P. J., McGuirk, J., Aldoss, I., Beitinjaneh, A. M., Muffly, L., Vij, R., Olsson, R. F., Byrne, M., Schultz, K. R., Aljurf, M., Seftel, M., Savoie, M. L., Savani, B. N., Verdonck, L. F., Cairo, M. S., Hossain, N., Bhatt, V. R., Frangoul, H. A., Abdel-Azim, H., Al Malki, M., Munker, R., Rizzieri, D., Khera, N., Nakamura, R., Ringden, O., Van der Poel, M., Murthy, H. S., Liu, H., Mori, S., De Oliveira, S., Bolanos-Meade, J., Elsawy, M., Barba, P., Nathan, S., George, B., Pawarode, A., Grunwald, M., Agrawal, V., Wang, Y., Assal, A., Caro, P. C., Kuwatsuka, Y., Seo, S., Ustun, C., Politikos, I., Lazarus, H. M., Saber, W., Sandmaier, B. M., De Lima, M., Litzow, M., Bachanova, V., Weisdorf, D. 2021; 106 (8): 2295-2296

  View details for DOI 10.3324/haematol.2021.279046

  View details for PubMedID 34333962

• CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nature medicine Spiegel, J. Y., Patel, S., Muffly, L., Hossain, N. M., Oak, J., Baird, J. H., Frank, M. J., Shiraz, P., Sahaf, B., Craig, J., Iglesias, M., Younes, S., Natkunam, Y., Ozawa, M. G., Yang, E., Tamaresis, J., Chinnasamy, H., Ehlinger, Z., Reynolds, W., Lynn, R., Rotiroti, M. C., Gkitsas, N., Arai, S., Johnston, L., Lowsky, R., Majzner, R. G., Meyer, E., Negrin, R. S., Rezvani, A. R., Sidana, S., Shizuru, J., Weng, W., Mullins, C., Jacob, A., Kirsch, I., Bazzano, M., Zhou, J., Mackay, S., Bornheimer, S. J., Schultz, L., Ramakrishna, S., Davis, K. L., Kong, K. A., Shah, N. N., Qin, H., Fry, T., Feldman, S., Mackall, C. L., Miklos, D. B. 2021

  Abstract

  Despite impressive progress, more than 50% of patients treated with CD19-targeting chimeric antigen receptor T cells (CAR19) experience progressive disease. Ten of 16 patients with large B cell lymphoma (LBCL) with progressive disease after CAR19 treatment had absent or low CD19. Lower surface CD19 density pretreatment was associated with progressive disease. To prevent relapse with CD19- or CD19lo disease, we tested a bispecific CAR targeting CD19 and/or CD22 (CD19-22.BB.z-CAR) in a phase I clinical trial ( NCT03233854 ) of adults with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL) and LBCL. The primary end points were manufacturing feasibility and safety with a secondary efficacy end point. Primary end points were met; 97% of products met protocol-specified dose and no dose-limiting toxicities occurred during dose escalation. In B-ALL (n=17), 100% of patients responded with 88% minimal residual disease-negative complete remission (CR); in LBCL (n=21), 62% of patients responded with 29% CR. Relapses were CD19-/lo in 50% (5 out of 10) of patients with B-ALL and 29% (4 out of 14) of patients with LBCL but were not associated with CD22-/lo disease. CD19/22-CAR products demonstrated reduced cytokine production when stimulated with CD22 versus CD19. Our results further implicate antigen loss as a major cause of CAR T cell resistance, highlight the challenge of engineering multi-specific CAR T cells with equivalent potency across targets and identify cytokine production as an important quality indicator for CAR T cell potency.

  View details for DOI 10.1038/s41591-021-01436-0

  View details for PubMedID 34312556

• Outcomes after delayed and second autologous stem cell transplant in patients with relapsed multiple myeloma. Bone marrow transplantation Lemieux, C., Muffly, L. S., Iberri, D. J., Craig, J. K., Johnston, L. J., Lowsky, R., Shiraz, P., Rezvani, A. R., Frank, M. J., Weng, W., Meyer, E., Shizuru, J. A., Arai, S., Liedtke, M., Negrin, R. S., Miklos, D. B., Sidana, S. 2021

  Abstract

  We evaluated the outcomes of 168 patients undergoing delayed or second autologous stem cell transplant (ASCT) for relapsed multiple myeloma (MM) from 2010 to 2019. Overall, 21% (n=35) patients had received a prior transplant and 69% (n=116) underwent transplant at first relapse. Overall, 27% patients had high-risk cytogenetics and 15% had ISS stage III disease. Stem cell collection was performed after relapse in 72% and 35% of patients received maintenance therapy. Median PFS from salvage treatment and transplant were 28 and 19 months, respectively. Median OS from salvage treatment and transplant was 69 and 55 months. Multivariate analysis revealed that ASCT in first relapse was associated with superior PFS (HR 0.63, p=0.03) and OS (HR 0.59, p=0.04) compared to later lines of therapy. In addition, PFS of ≥36 months with prior therapy was associated with improved PFS (HR 0.62, p=0.04) and OS (HR 0.41, p=0.01). Ninety-five patients underwent delayed transplant at first relapse, median PFS and OS from start of therapy was 30 and 69 months, and median OS from diagnosis was 106 months. These data may serve as a guide when counseling patients undergoing ASCT for relapsed MM and provide a benchmark in designing clinical trials of transplantation/comparative treatments for relapsed MM.

  View details for DOI 10.1038/s41409-021-01371-1

  View details for PubMedID 34163014

• Inferior Clinical Outcomes in Recipients of Cryopreserved Grafts Following Reduced Intensity Allogeneic Hematopoietic Cell Transplantation: A Single Center Report Bankova, A., Caveney, J., Ramos, T., Bogeholz, J., Heydari, K., Diaz, N., Jackson, M., Lowsky, R., Brown, J., Johnston, L., Rezvani, A., Frank, M., Muffly, L., Weng, W., Sidana, S., Negrin, R., Miklos, D., Shiraz, P., Meyer, E., Shizuru, J., Arai, S. SPRINGERNATURE. 2021: 181

  View details for Web of Science ID 000668928500152

• Phase 2 study of MGTA-145+plerixafor for rapid and reliable hematopoietic stem cell (HSC) mobilization for autologous transplant in multiple myeloma. Sidana, S., Bankova, A., Hosoya, H., Muffly, L. S., Kumar, S., Johnston, L. J., Lowsky, R., Meyer, E., Rezvani, A., Weng, W., Arai, S., Frank, M., Shiraz, P., Howell, H., Goncalves, K. A., Schmelmer, V., Davis, J., Shizuru, J., Miklos, D. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.8023

  View details for Web of Science ID 000708120604186

• Implementation of a clinic to facilitate the transition from pediatric to adult cancer survivorship care. Smith, S. M., Jin, A., Simon, P., Clayton, A., Benedict, C., Liedtke, M., Muffly, L. S., Schapira, L. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e13519

  View details for Web of Science ID 000708120300199

• Event free survival in adults with relapsed ALL who underwent front-line therapy with CALGB 10403. Raychaudhuri, S., Yurkiewicz, I., Mannis, G. N., Medeiros, B. C., Coutre, S. E., Muffly, L. S., Liedtke, M. LIPPINCOTT WILLIAMS & WILKINS. 2021

  View details for DOI 10.1200/JCO.2021.39.15_suppl.e19005

  View details for Web of Science ID 000708120304096

• Chronic medical conditions and late effects after acute myeloid leukaemia in adolescents and young adults: a population-based study. International journal of epidemiology Abrahao, R., Huynh, J. C., Benjamin, D. J., Li, Q. W., Winestone, L. E., Muffly, L., Keegan, T. H. 2021; 50 (2): 663-674

  Abstract

  BACKGROUND: Curative-intent treatment of acute myeloid leukaemia (AML) can lead to multiple chronic medical conditions ('late effects'). Little is known about the burden of late effects in adolescent and young adult (AYA, 15-39years) survivors of AML. We aimed to estimate the cumulative incidence and investigate the main predictors of late effects among these patients.METHODS: During 1996-2012, 1168 eligible AYAs with AML who survived ≥2years after diagnosis were identified in the California Cancer Registry. Late effects were reported from State hospital discharge data, and patients were followed through 2014. Hazard ratios and 95% confidence intervals of late effects occurrence were estimated using Cox proportional hazard models, adjusted for sociodemographic and clinical factors.RESULTS: The most common late effects at 10years after diagnosis were: endocrine (26.1%), cardiovascular (18.6%) and respiratory (6.6%), followed by neurologic (4.9%), liver/pancreatic (4.3%), renal (3.1%), avascular necrosis (2.7%) and second primary malignancies (2.4%). Of 1168 survivors, 547 (46.8%) received a haematopoietic stem cell transplant (HSCT). After multivariable adjustments, AYAs who underwent HSCT or had a non-favourable risk AML experienced 2-fold or higher increased likelihood of all late effects. Additionally, AYAs of Hispanic, Black or Asian/Pacific Islander (vs non-Hispanic White) race/ethnicity and those who resided in lower socio-economic neighbourhoods were at higher risk of numerous late effects.CONCLUSIONS: Our findings underscore the need for long-term surveillance for the prevention, early detection and treatment of late effects, and can inform the development of AYA-focused consensus-based guidelines that will ultimately improve the quality of life and survival of these young vulnerable patients.

  View details for DOI 10.1093/ije/dyaa184

  View details for PubMedID 34000732

• Stem Cell Mobilization in Multiple Myeloma: Comparing Safety and Efficacy of Cyclophosphamide +/- Plerixafor vs. G-CSF +/- Plerixafor in the Lenalidomide Era. Transplantation and cellular therapy Johnsrud, A., Ladha, A., Muffly, L., Shiraz, P., Goldstein, G., Osgood, V., Shizuru, J. A., Johnston, L., Arai, S., Weng, W., Lowsky, R., Rezvani, A. R., Meyer, E. H., Frank, M. J., Negrin, R. S., Miklos, D. B., Sidana, S. 2021

  Abstract

  Growth factor and chemotherapy-based stem cell mobilization strategies are commonly used for patients with multiple myeloma. We retrospectively compared 398 patients mobilized between 2017-2020 using either cyclophosphamide (4g/m2) plus granulocyte colony stimulating factor (GCSF) or G-CSF alone, with on demand plerixafor (PXF) in both groups. While total CD34+yield was higher after chemo-mobilization compared to GCSF+/-PXF (median 13.6 vs. 4.4 * 106/kg,P< .01), achievement of≥2 * 106CD34+ cells (95% vs 93.7%,P= .61), and rates of mobilization failure (5% vs. 6.3%,P= .61) were similar. Fewer patients required PXF with chemo-mobilization (12.3% vs 49.5%,P< .01), and apheresis sessions were fewer (median: 1, range 1-4 vs. 2, range 1-5). Complications were higher after chemo-mobilization (30% vs. 7.4%,P< .01), including neutropenic fever, ED visits, and hospitalizations. Prior lenalidomide≤6 cycles did not impair cell yield in either group.Median cost of mobilization was 17.4% lower in the GCSF +/- PXF group (P= .01).Differences in time to engraftment were not clinically significant. Given similar rates mobilization success, engraftment time, and less toxicity and lower costs compared to chemo-mobilization, G-CSF with on-demand PXF may be preferable in myeloma patients with adequate disease control and limited lenalidomide exposure.

  View details for DOI 10.1016/j.jtct.2021.04.016

  View details for PubMedID 33915323

• Return to Work Among Young Adult Survivors of Allogeneic Hematopoietic Cell Transplantation in the United States. Transplantation and cellular therapy Bhatt, N. S., Brazauskas, R., Salit, R. B., Syrjala, K., Bo-Subait, S., Tecca, H., Badawy, S. M., Baker, K. S., Beitinjaneh, A., Bejanyan, N., Byrne, M., Dias, A., Farhadfar, N., Freytes, C. O., Ganguly, S., Hashmi, S., Hayashi, R. J., Hong, S., Inamoto, Y., Jamani, K., Kasow, K. A., Khera, N., Krem, M. M., Lazarus, H. M., Lee, C. J., Lee, S., Majhail, N. S., Malone, A. K., Marks, D. I., Mau, L., Mayo, S. J., Muffly, L. S., Nathan, S., Nishihori, T., Page, K. M., Preussler, J., Rangarajan, H. G., Rotz, S. J., Salooja, N., Savani, B. N., Schears, R., Schechter-Finkelstein, T., Schiller, G., Shah, A. J., Sharma, A., Wang, T., Wirk, B., Battiwalla, M., Schoemans, H., Hamilton, B., Buchbinder, D., Phelan, R., Shaw, B. 2021

  Abstract

  BACKGROUND: Young adult (YA) survivors of allogeneic hematopoietic cell transplant (HCT) are at risk for late psychosocial challenges, including inability to return to work post-HCT. However, work-related outcomes in this population remain understudied.OBJECTIVES: To assess the post-HCT work status of survivors of allogeneic HCT who underwent HCT as YA and analyze the patient-, disease-, and HCT-related factors associated with their work status at 1-year post-HCT.STUDY DESIGN: Using the Center for International Blood and Marrow Transplant Research (CIBMTR) data, we described post-HCT work status (full-time, part-time work, unemployed, and medical disability) of YA HCT survivors (N=1365) who underwent HCT between 2008 and 2015. Percentages of work status categories were reported at four timepoints: 6-months, 1-, 2-, and 3-year post-HCT. Percentages of post-HCT work status categories at the 1-year timepoint were also described in relation to survivors' pre-HCT work status categories. Factors associated with 1-year post-HCT work status (full-time or part-time work) were examined using logistic regression.RESULTS: From 6 months to 3 years post-HCT, the percentage of survivors working full-time and part-time increased from 18.3% to 50.7%, and from 6.9% to 10.5%, respectively. Of patients in full-time work pre-HCT, 50% were unemployed or on medical disability at 1-year post-HCT. Female sex (Odds ratio [OR] 0.55; 95% confidence interval [CI] 0.40-0.77), HCT-comorbidity index (HCT-CI) score ≥3 (OR 0.57; 95% CI 0.39-0.82), pre-HCT unemployment (OR 0.37; 95% CI 0.24-0.56), and medical disability (OR 0.44; 95% CI 0.28-0.70), development of grade 3-4 acute graft vs. host disease (OR 0.52; 95% CI 0.34-0.80), and relapse within one-year post-HCT (OR 0.34; 95% CI 0.21-0.56) were associated with lower likelihood of employment at 1-year post-HCT. Compared to myeloablative conditioning with total body irradiation (TBI), myeloablative conditioning without TBI (OR 1.71; 95% CI 1.16-2.53) was associated with higher likelihood of employment at 1-year post-HCT. Graduate school level education (OR 2.47; 95% CI 1.49-4.10) was also associated with higher likelihood of employment at 1-year post-HCT.CONCLUSIONS: While the work status among YA HCT survivors continued to improve over time, a substantial subset became or remained unemployed or on medical disability. These findings underscore the need for effective return to work supportive interventions in this population.

  View details for DOI 10.1016/j.jtct.2021.04.013

  View details for PubMedID 33895402

• Prospective Randomized Study of Advance Directives in Allogeneic Hematopoietic Cell Transplant Recipients. Transplantation and cellular therapy Tan, I. T., Sundaram, V., Ramirez, Y., Burnash, S., Kate Tierney, D., Muffly, L. S. 2021

  Abstract

  BACKGROUND: Patients undergoing allogeneic HCT are at risk for high morbidity and mortality. Advance directives (AD) allow patients to express wishes regarding their care at the end of life, but these are not completed in the majority of patients undergoing HCT, with only 44% of deceased allogeneic HCT recipients at this institution completing an AD in the past decade. Increasing AD completion rate can improve quality of care for allogeneic HCT recipients.OBJECTIVE: Evaluating whether an alternative AD instrument can increase AD completion rate and patient satisfaction.STUDY DESIGN: We conducted a prospective, randomized controlled study of the traditional California AD vs. the use of a novel Letter AD, the Stanford What Matters Most Letter, in adult allogeneic HCT recipients. Patients 18 years and older undergoing first allogeneic HCT at Stanford University were eligible. Prior to HCT conditioning, enrolled patients were randomly assigned to complete either the traditional AD or the Letter AD. The primary endpoint was AD completion; the chi-squared test was used to compare the AD completion rate between arms. Wilcoxon rank-sum tests were used to compare uncertainty, satisfaction with decision-making, and satisfaction with the AD.RESULTS: Of the total 212 patients who were eligible, 126 (59.4%) were enrolled and randomized. The mean age was 53.7 years; 57(45.2%) were female; 74 (58.7%) were non-Hispanic White. The overall AD completion rate was 71.4% and did not differ between the traditional and Letter AD arms (70.3% vs 72.6%, P= 0.78). Of those who completed the Letter AD, 66.7%, 42.2%, and 46.7% of patients wished to die gently/naturally, at home, and/or with hospice, respectively. The traditional AD found that 62.2% wished to not prolong life if recovery was unlikely. Opinion surveys did not find differences in levels of satisfaction between the traditional and Letter AD.CONCLUSION: Completion rates of AD on this study were high (71.4%) in comparison to historically reported completion rates and did not significantly differ based upon AD version.

  View details for DOI 10.1016/j.jtct.2021.03.030

  View details for PubMedID 33836311

• Azacitidine maintenance after allogeneic hematopoietic cell transplantation for MDS and AML. Blood advances El Chaer, F., Borate, U., Dulery, R., Holtan, S. G., Law, A. D., Muffly, L., Nassereddine, S., Shallis, R. M., Stringaris, K., Taylor, J., Devine, S. M., Mohty, M., Hourigan, C. S. 2021; 5 (6): 1757–59

  View details for DOI 10.1182/bloodadvances.2020003839

  View details for PubMedID 33755090

• Use of Backup Stem Cells for Stem Cell Boost and Second Transplant in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation. Transplantation and cellular therapy Liang, E. C., Muffly, L. S., Shiraz, P., Shizuru, J. A., Johnston, L., Arai, S., Frank, M. J., Weng, W., Lowsky, R., Rezvani, A., Meyer, E. H., Negrin, R., Miklos, D. B., Sidana, S. 2021

  Abstract

  Autologous hematopoietic stem cell transplantation (ASCT) is a standard treatment for multiple myeloma (MM). Consensus guidelines recommend collecting sufficient stem cells in case there is a need for stem cell boost for delayed/poor engraftment or for future second ASCT. However, collecting and storing backup stem cells in all patients requires significant resources and cost, and the rates of backup stem cell utilization are not well studied. We sought to examine the utilization of backup stem cells (BSCs) in patients with MM undergoing ASCT. Patients with MM aged ≥18 years old who underwent first ASCT at our institution from January 2010 through December 2015 and collected sufficient stem cells for at least 2 transplants were included in this single-center retrospective study. This timeframe was selected to allow for adequate follow-up. A total of 393 patients were included. The median age was 58 years (range, 25-73). After a median follow-up of 6 years, the median progression-free survival (PFS) of the cohort was 3 years. Sixty-one percent (n=240) of patients progressed or relapsed. Chemotherapy-based mobilization was used in almost all patients (98%). The median total CD34+ cells collected was 18.2*106/kg (range, 3.4-112.4). A median of 5.7*106 CD34+ cells/kg (range, 1.8-41.9) was infused during the first ASCT, and a median of 10.1*106 CD34+ cells/kg (range, 1.5-104.5) was cryopreserved for future use. Of the patients, 6.9% (n=27) used backup stem cells, with 2.3% (n=10) using them for stem cell boost, 4.6% (n=18) for a second salvage ASCT, including 1 patient for both stem cell boost and second ASCT. Rates of backup stem cell use among patients aged <60, 60-69, and ≥70 years were 7.8%, 5.7%, and 5.9%, respectively. There was a trend toward higher rates of backup stem cell use for second ASCT in patients who were younger, had suboptimal disease control at time of first ASCT, and longer PFS. The median dose of stem cell boost given was 5.6*106 CD34+ cells/kg (range, 1.9-20). The median time from stem cell boost to neutrophil, hemoglobin, and platelet engraftment was 4 (range, 2-11), 15 (range, 4-34), and 12 (range, 0-34) days, respectively. Lower CD34+ dose and older age at time of ASCT predicted need for stem cell boost. With new salvage therapies for relapsed MM, the rates of second ASCT are very low. The low rates of use suggest that institutional policies regarding universal BSC collection and long-term storage should be reassessed and individualized. However, need for stem cell boost in 2.3% of patients may present a challenge to that.

  View details for DOI 10.1016/j.jtct.2021.02.026

  View details for PubMedID 33775587

• Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma. Blood advances Baird, J. H., Epstein, D. J., Tamaresis, J. S., Ehlinger, Z., Spiegel, J. Y., Craig, J., Claire, G. K., Frank, M. J., Muffly, L., Shiraz, P., Meyer, E., Arai, S., Brown, J. W., Johnston, L., Lowsky, R., Negrin, R. S., Rezvani, A. R., Weng, W. K., Latchford, T., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S. 2021; 5 (1): 143-155

  Abstract

  Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has significantly improved outcomes in the treatment of refractory or relapsed large B-cell lymphoma (LBCL). We evaluated the long-term course of hematologic recovery, immune reconstitution, and infectious complications in 41 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) at a single center. Grade 3+ cytopenias occurred in 97.6% of patients within the first 28 days postinfusion, with most resolved by 6 months. Overall, 63.4% of patients received a red blood cell transfusion, 34.1% of patients received a platelet transfusion, 36.6% of patients received IV immunoglobulin, and 51.2% of patients received growth factor (granulocyte colony-stimulating factor) injections beyond the first 28 days postinfusion. Only 40% of patients had recovered detectable CD19+ B cells by 1 year, and 50% of patients had a CD4+ T-cell count <200 cells per μL by 18 months postinfusion. Patients with durable responses to axi-cel had significantly longer durations of B-cell aplasia, and this duration correlated strongly with the recovery of CD4+ T-cell counts. There were significantly more infections within the first 28 days compared with any other period of follow-up, with the majority being mild-moderate in severity. Receipt of corticosteroids was the only factor that predicted risk of infection in a multivariate analysis (hazard ratio, 3.69; 95% confidence interval, 1.18-16.5). Opportunistic infections due to Pneumocystis jirovecii and varicella-zoster virus occurred up to 18 months postinfusion in patients who prematurely discontinued prophylaxis. These results support the use of comprehensive supportive care, including long-term monitoring and antimicrobial prophylaxis, beyond 12 months after axi-cel treatment.

  View details for DOI 10.1182/bloodadvances.2020002732

  View details for PubMedID 33570626

• Immune reconstitution and infectious complications following axicabtagene ciloleucel therapy for large B-cell lymphoma BLOOD ADVANCES Baird, J. H., Epstein, D. J., Tamaresis, J. S., Ehlinger, Z., Spiegel, J. Y., Craig, J., Claire, G. K., Frank, M. J., Muffly, L., Shiraz, P., Meyer, E., Arai, S., Brown, J., Johnston, L., Lowsky, R., Negrin, R. S., Rezvani, A. R., Weng, W., Latchford, T., Sahaf, B., Mackall, C. L., Miklos, D. B., Sidana, S. 2021; 5 (1): 143–55

  View details for DOI 10.1182/bloodadvances.2020002732

  View details for Web of Science ID 000607932700016

• Incidence and Risk Factors Associated with Bleeding and Thrombosis Following Chimeric Antigen Receptor T Cell Therapy. Blood advances Johnsrud, A. J., Craig, J., Baird, J. H., Spiegel, J. Y., Muffly, L., Zehnder, J. L., Tamaresis, J. S., Negrin, R. S., Johnston, L., Arai, S., Shizuru, J. A., Lowsky, R., Meyer, E., Weng, W. K., Shiraz, P., Rezvani, A. R., Latchford, T., Mackall, C. L., Miklos, D. B., Frank, M. J., Sidana, S. 2021

  Abstract

  Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (n=127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated between 2017-2020 with axicabtagene ciloleucel (axi-cel) (N=89) or a bispecific CD19/CD22 CAR (N=38). 12 (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8-30 (median 17.5), and thrombosis between days 2-91 (median 29). Bleeding sites included genitourinary (N=6), soft tissue (N=2), intracranial (N=2), gastrointestinal (N=1), pulmonary (N=1), and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older (median 72 vs. 60 yrs, P<0.01), had lower baseline platelets (86 vs. 178 K/uL, P<0.01), lower platelet nadir after CAR-T (median 17.5 vs. 48 K/uL; P<0.01), lower fibrinogen nadir (median 122 vs. 340 ug/mL; P<0.01) and elevated LDH (P=0.01). ICANS grade ≥3 was associated with increased bleeding (50% vs. 15%; P=0.01), thrombosis (50% vs. 16%; P=0.04), PT prolongation, hypofibrinogenemia and elevated D-dimer. A paucity of events limited multivariate analysis, however low pre-treatment platelets were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding complications and should be closely monitored particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR-T therapy, including their association with neurotoxicity.

  View details for DOI 10.1182/bloodadvances.2021004716

  View details for PubMedID 34521106

• Measurable residual disease status and FLT3 inhibitor therapy in patients with FLT3-ITD mutated AML following allogeneic hematopoietic cell transplantation. Bone marrow transplantation Liang, E. C., Chen, C., Lu, R., Mannis, G. N., Muffly, L. 2021

  Abstract

  Measurable residual disease (MRD) is associated with poor prognosis in acute myeloid leukemia (AML), even after allogeneic hematopoietic cell transplantation (HCT). New next-generation sequencing (NGS) methods have emerged as a highly sensitive and specific method to detect MRD. In addition to defining the role of post-HCT MRD monitoring in FLT3-ITD mutated AML, there is great interest in the optimal use of oral FLT3 tyrosine kinase inhibitors (FLT3 inhibitors) to maintain remission following HCT. In this study, we evaluated the clinical impact of sensitive FLT3 MRD testing early after HCT and maintenance FLT3 inhibitor use at our transplant center. We found that there was a trend towards inferior progression-free survival (PFS) for patients with early post-HCT MRD, but that overall survival (OS) was not significantly impacted by MRD. The use of maintenance FLT3 inhibitors led to a significantly superior PFS and OS in our cohort, and improved PFS and OS in both MRD-negative and MRD-positive patients. Altogether, our results demonstrate the prognostic significance of NGS-based MRD monitoring for FLT3-ITD and the ability of post-HCT maintenance therapy to prevent relapse and death in FLT3-ITD mutated AML.

  View details for DOI 10.1038/s41409-021-01475-8

  View details for PubMedID 34584238

• Adding Centralized Electronic Patient-Reported Outcome Data Collection to an Established International Clinical Outcomes Registry. Transplantation and cellular therapy Cusatis, R., Flynn, K. E., Vasu, S., Pidala, J., Muffly, L., Uberti, J., Tamari, R., Mattila, D., Mussetter, A., Bruzauskas, R., Chen, M., Leckrone, E., Myers, J., Mau, L. W., Rizzo, J. D., Saber, W., Horowitz, M., Lee, S. J., Burns, L. J., Shaw, B. 2021

  Abstract

  The importance of patient-reported outcomes (PROs) in cellular therapies, including hematopoietic cell transplantation (HCT) is highlighted in this study. Longitudinal collection of PROs in a registry is recommended for several reasons, yet to date, PROs are not routinely collected from HCT patients to augment clinical registry data. The aim of this study was to determine the feasibility of electronic PRO data collection by a national clinical outcomes registry, by assessing differences between who does and does not report PROs. We conducted a cross-sectional pilot collection of PROs from HCT recipients after treatment using computer-adapted tests from the Patient-Reported Outcome Measurement Information System (PROMIS). We implemented centralized data collection through the Center for International Blood and Marrow Transplant Research (CIBMTR) among patients who underwent HCT for myelodysplastic syndromes (MDS), were at least 6 months post-HCT, and spoke English or Spanish. The main objective was identifying patient, disease, and transplant-related differences associated with completion of electronic PROs. Patients were excluded from analysis if they were determined to be ineligible (deceased, did not speak English or Spanish, refused to be contacted by the CIBMTR). A total of 163 patients were contacted and potentially eligible to participate; of these, 92 (56%) enrolled and 89 (55%) completed the PRO assessment. The most frequent reason for incomplete surveys was inability to contact patients (n = 88), followed by declining to participate in the study (n = 37). There were no sociodemographic or age differences between those who completed the PRO survey (n = 89) and eligible nonresponders (n = 155). Patient scores were within 3 points of the US average of 50 for all symptoms and functioning except physical functioning. Responders and nonresponders did not exhibit meaningfully different sociodemographic characteristics. Difficulty contacting patients posed the greatest barrier and also provided the greatest opportunity for improvement. Once enrolled, survey completion was high. These results support standardizing centralized PRO data collection through the CIBMTR registry.

  View details for DOI 10.1016/j.jtct.2021.10.016

  View details for PubMedID 34757219

• Routine use of gemtuzumab ozogamicin in 7 + 3-based inductions for all 'non-adverse' risk AML. Leukemia & lymphoma Ladha, A. n., Hui, G. n., Cheung, E. n., Berube, C. n., Coutre, S. E., Gotlib, J. n., Liedtke, M. n., Zhang, T. Y., Muffly, L. n., Mannis, G. N. 2021: 1–6

  View details for DOI 10.1080/10428194.2021.1876869

  View details for PubMedID 33491527

• Allogeneic hematopoietic cell transplantation (alloHCT) for patients over 65 years old is not associated with worse symptoms/function than younger patients - a Center for International Blood and Marrow Transplant Research (CIBMTR) study Shaw, B., Brazauskas, R., Burns, L. J., Mattila, D., Musseter, A., Chen, M., Vasu, S., Pidala, J., Muffly, L., Uberti, J., Tamari, R., Tamari, R., Leckrone, E., Myers, J., Mau, L., Rizzo, J., Saber, W., Horowitz, M. M., Lee, S. J., Flynn, K. E. SPRINGER. 2020: S29

  View details for Web of Science ID 000584632700070

• Outcomes with Autologous or Allogeneic Stem Cell Transplantation in Patients with Plasma Cell Leukemia in the Era of Novel Agents. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Lemieux, C., Johnston, L. J., Lowsky, R., Muffly, L. S., Craig, J. K., Shiraz, P., Rezvani, A., Frank, M. J., Weng, W., Meyer, E., Shizuru, J., Arai, S., Negrin, R., Miklos, D. B., Sidana, S. 2020

  Abstract

  Plasma cell leukemia (PCL) is a rare and very aggressive plasma cell disorder. The optimal treatment approach, including whether to pursue an autologous (autoSCT) or allogeneic (alloSCT) transplant is not clear as there is lack of clinical trial based evidence. This single center retrospective study describes the outcomes of 16 patients with PCL (N=14 primary PCL) who underwent either autoSCT (N=9) or alloSCT (N=7) for PCL in the era of novel agents, between 2007 and 2019. Median age of the cohort was 58 years. High-risk cytogenetics were seen in 50% of patients. All patients received a proteasome inhibitor (PI) and/or immunomodulatory drug (IMiD) based regimen before transplant. At transplant, 10 (62%) patients obtained at least a very good partial response. Response after autoSCT (3 month) was at least VGPR in 6 (67%, CR=5) patients. All patients undergoing alloSCT achieved CR at 3 months. Maintenance was used in 5 patients (56%) after autoSCT. Median PFS from transplant in the autoSCT vs. alloSCT group was 6 vs. 18 months, p=0.09, while median OS from transplant was 19 vs. 40 months (p=0.41), respectively. The median OS from diagnosis was 27 vs. 49 months, p=0.50, respectively. Of all the deaths, 10 (91%) patients died of relapsed disease. In conclusion, alloSCT was not observed to offer any significant survival advantage over autoSCT in PCL, which is comparable to other recent reports and relapse remains the primary cause of death.

  View details for DOI 10.1016/j.bbmt.2020.08.035

  View details for PubMedID 32961371

• How I Approach the Patient Who Has MRD or Relapse After Transplant CLINICAL LYMPHOMA MYELOMA & LEUKEMIA Muffly, L. 2020; 20: S32–S33

  View details for Web of Science ID 000564055100015

• Late Effects in Survivors of Adolescent and Young Adult Acute Lymphoblastic Leukemia. JNCI cancer spectrum Muffly, L., Maguire, F. B., Li, Q., Kennedy, V., Keegan, T. H. 2020; 4 (4): pkaa025

  Abstract

  Background: Knowledge regarding late effects (medical conditions and subsequent neoplasms) in survivors of adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) is lacking.Methods: Using the population-based California Cancer Registry linked with California hospitalization data, we evaluated late effects in 1069 AYAs (aged 15-39years) diagnosed with ALL in California between 1995 and 2012 and surviving a minimum of 3 years from diagnosis.Results: The estimated 10-year cumulative incidence of subsequent endocrine disease (28.7%, 95% confidence interval [CI] = 25.8% to 31.6%) and cardiac disease (17.0%, 95% CI = 14.6% to 19.5%) were strikingly high; avascular necrosis (9.6%, 95% CI = 7.8% to 11.6%), liver disease (6.5%, 95% CI = 5.0% to 8.3%), respiratory disease (6.2%, 95% CI = 4.8% to 8.0%), seizure and/or stroke (4.3%, 95% CI = 3.1% to 5.8%), renal disease (3.1%, 95% CI = 2.1% to 4.4%), and second neoplasms (1.4%, 95% CI = 0.7% to 2.4%) were estimated to occur at 10years with the reported frequencies. Multivariable analyses including the entire patient cohort demonstrated that public or no insurance (vs private and/or military insurance) and receipt of hematopoietic cell transplantation were independently associated with the occurrence of all late effects considered. In multivariable analyses limited to the 766 AYAs who were not transplanted, we continued to find a statistically significant association between public and no insurance and the occurrence of all late effects. Frontline regimen type (pediatric vs adult) was not statistically significantly associated with any of the late effect categories.Conclusions: This large population-based analysis is among the first to describe late effects in survivors of AYA ALL. The strong association between insurance type and late effects suggests that AYAs with public or no insurance may have reduced access to survivorship care following completion of ALL therapy.

  View details for DOI 10.1093/jncics/pkaa025

  View details for PubMedID 32704618

• Philadelphia chromosome positive acute lymphoblastic leukemia in adults: Therapeutic options and dilemmas in 2020. Seminars in hematology Muffly, L., Kebriaei, P. 2020; 57 (3): 137–41

  Abstract

  The incorporation of tyrosine kinase inhibitors (TKI) into front-line therapy for adults with Philadelphia chromosome positive acute lymphoblastic leukemia has dramatically altered response rates and significantly improved outcomes, such that this entity may no longer be considered a high risk acute lymphoblastic leukemia subgroup. In this review article, we summarize approaches to front-line therapy in the TKI era, including intensive chemotherapy-based regimens and deintensified therapy. We also review optimal disease monitoring strategies, discuss the role of consolidative hematopoietic cell transplantation, and touch on options for relapsed disease. The incorporation of novel targeted agents in conjunction with TKIs into front-line therapy will likely alter the future therapeutic approaches to this disease.

  View details for DOI 10.1053/j.seminhematol.2020.09.002

  View details for PubMedID 33256903

• Impact of proteasome inhibitor vs. IMiD maintenance therapy on outcomes of patients with high-risk multiple myeloma (HRMM). Tam, E., Iberri, D., Liedtke, M., Muffly, L. S., Shiraz, P., Frank, M., Lowsky, R., Rezvani, A., Negrin, R., Meyer, E., Arai, S., Johnston, L. J., Shizuru, J., Weng, W., Miklos, D., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307484

• Autologous stem cell transplantation versus no transplant in patients above 70 with multiple myeloma. Lemieux, C., Muffly, L. S., Iberri, D., Rezvani, A., Lowsky, R., Frank, M., Craig, J. K., Liedtke, M., Negrin, R., Weng, W., Meyer, E., Johnston, L. J., Shizuru, J., Shiraz, P., Arai, S., Miklos, D., Sidana, S. LIPPINCOTT WILLIAMS & WILKINS. 2020

  View details for Web of Science ID 000560368307442

• Hematopoietic Cell Transplantation for Philadelphia Chromosome Negative Adult Acute Lymphoblastic Leukemia in the Modern Era of Immune Therapy. Current hematologic malignancy reports Yurkiewicz, I., Craig, J., Muffly, L. 2020

  Abstract

  PURPOSE OF REVIEW: This review will discuss the data and controversies related to HCT in the front-line and relapsed/refractory setting in the context of newly available targeted immunotherapies.RECENT FINDINGS: Recent studies in adult Ph-negative ALL support the use of measurable residual disease (MRD) response to front-line therapy to guide consolidation. As such, most MRD-negative patients do not require front-line HCT. Blinatumomab benefits patients with B-ALL with MRD+ complete response (CR) and can be used as a bridge to HCT; whether HCT is still required in this setting is an area of ongoing inquiry. Blinatumomab and inotuzumab result in high rates of MRD negative CR in adults with relapsed/refractory ALL and allow more patients with relapsed disease to receive HCT. Chimeric antigen receptor T cell (CAR-T) therapies may serve as a bridge to HCT or as a stand-alone therapy for relapsed/refractory patients; data suggests there may be greater benefit to consolidating CAR-T with HCT in HCT-naive adults. The decision to incorporate consolidative allogeneic HCT into front-line therapy should be primarily guided by MRD status and the ALL regimen utilized. Targeted immunotherapies result in high MRD-negative CR rates, allowing more adults with relapsed/refractory ALL to be successfully bridged to HCT; early incorporation of these therapies may also prove valuable in reducing the need for HCT in the front-line setting by increasing MRD negative CR rates.

  View details for DOI 10.1007/s11899-020-00579-0

  View details for PubMedID 32358681

• Access to specialized care and outcomes in adults with acute leukemias BLOOD ADVANCES Muffly, L., Bhatt, V. R. 2020; 4 (7): 1538

  View details for Web of Science ID 000526961000042

• Access to specialized care and outcomes in adults with acute leukemias. Blood advances Muffly, L., Bhatt, V. R. 2020; 4 (7): 1538

  View details for DOI 10.1182/bloodadvances.2019000660

  View details for PubMedID 32289165

• Late effects after ablative allogeneic stem cell transplantation for adolescent and young adult acute myeloid leukemia. Blood advances Lee, C. J., Kim, S., Tecca, H. R., Bo-Subait, S., Phelan, R., Brazauskas, R., Buchbinder, D., Hamilton, B. K., Battiwalla, M., Majhail, N. S., Lazarus, H. M., Shaw, P. J., Marks, D. I., Litzow, M. R., Chhabra, S., Inamoto, Y., DeFilipp, Z., Hildebrandt, G. C., Olsson, R. F., Kasow, K. A., Liesveld, J. L., Rotz, S. J., Badawy, S. M., Bhatt, N. S., Yared, J. A., Page, K. M., Arellano, M. L., Kent, M., Farhadfar, N., Seo, S., Hematti, P., Freytes, C. O., Rovo, A., Ganguly, S., Nathan, S., Burns, L., Shaw, B. E., Muffly, L. S. 2020; 4 (6): 983–92

  Abstract

  There is marked paucity of data regarding late effects in adolescents and young adults (AYAs) who undergo myeloablative conditioning (MAC) allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML). We evaluated late effects and survival in 826 1-year disease-free survivors of MAC HCT for AYA AML, with an additional focus on comparing late effects based upon MAC type (total body irradiation [TBI] vs high-dose chemotherapy only). The estimated 10-year cumulative incidence of subsequent neoplasms was 4% (95% confidence interval [CI], 2%-6%); 10-year cumulative incidence of nonmalignant late effects included gonadal dysfunction (10%; 95% CI, 8%-13%), cataracts (10%; 95% CI, 7%-13%), avascular necrosis (8%; 95% CI, 5%-10%), diabetes mellitus (5%; 95% CI, 3%-7%), and hypothyroidism (3%; 95% CI, 2%-5%). Receipt of TBI was independently associated with a higher risk of cataracts only (hazard ratio [HR], 4.98; P < .0001) whereas chronic graft-versus-host disease (cGVHD) was associated with an increased risk of cataracts (HR, 3.22; P = .0006), avascular necrosis (HR, 2.49; P = .006), and diabetes mellitus (HR, 3.36; P = .03). Estimated 10-year overall survival and leukemia-free survival were 73% and 70%, respectively, and did not differ on the basis of conditioning type. In conclusion, late effects among survivors of MAC HCT for AYA AML are frequent and are more closely linked to cGVHD than type of conditioning.

  View details for DOI 10.1182/bloodadvances.2019001126

  View details for PubMedID 32168378

• The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia. International journal of molecular sciences Shiraz, P., Payne, K. J., Muffly, L. 2020; 21 (6)

  Abstract

  Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is a high-risk B-cell Acute Lymphoblastic Leukemia (B-ALL) characterized by a gene expression profile similar to Ph-positive B-ALL but lacking the BCR-ABL1 translocation. The molecular pathogenesis of Ph-like B-ALL is heterogenous and involves aberrant genomics, receptor overexpression, kinase fusions, and mutations leading to kinase signaling activation, leukemogenic cellular proliferation, and differentiation blockade. Testing for the Ph-like signature, once only a research technique, is now available to the clinical oncologist. The plethora of data pointing to poor outcomes for this ALL subset has triggered investigations into the role of targeted therapies, predominantly involving tyrosine kinase inhibitors that are showing promising results.

  View details for DOI 10.3390/ijms21062193

  View details for PubMedID 32235787

• Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era Muffly, L., Arai, S., Johnston, L., Lowsky, R., Meyer, E. H., Miklos, D. B., Negrin, R. S., Rezvani, A., Shiraz, P., Shizuru, J. A., Sidana, S., Weng, W., Cunanan, K. ELSEVIER SCIENCE INC. 2020: S106

  View details for Web of Science ID 000516887900144

• Clinical actionability of measurable residual disease (MRD) assessment in the management of patients with hematologic malignancies: a case-based monograph. Clinical advances in hematology & oncology : H&O Wolf, J., Fonseca, R., Muffly, L. 2020; 18 Suppl 9 (3): 1-16

  Abstract

  New treatments for hematologic malignancies have led to outcomes that are outpacing the ability of traditional measures of response to accurately capture a patient's depth of response and risk of relapse. Assessment of measurable residual disease (MRD) offers a high-sensitivity evaluation for remaining disease present in a patient. MRD is not a surrogate marker for the detection of cancer cells, but rather a direct measure of them. MRD has quickly become an important measurement of response in patients with multiple myeloma and acute lymphocytic leukemia. Retrospective and prospective studies indicate that MRD-negative patients have better outcomes, particularly progression-free and overall survival, compared with patients who are MRD-positive. Two methods have emerged as the primary strategies for assessing MRD: next-generation sequencing (NGS) and next-generation flow (NGF). Both methods measure detectable disease in the bone marrow. The clonoSEQ® Assay, which uses NGS technology, is cleared by the US Food and Drug Administration for the detection and monitoring of MRD in bone marrow samples from patients with multiple myeloma or B-cell acute lymphoblastic leukemia. This monograph discusses the supporting research and clinical use of MRD assessment among patients with multiple myeloma and acute lymphoblastic leukemia.

  View details for PubMedID 33843875

• Assessment of measurable residual disease (MRD) in adult patients with acute lymphocytic leukemia: best use and a case report. Clinical advances in hematology & oncology : H&O Muffly, L. 2020; 18 Suppl 9 (3): 10-14

  View details for PubMedID 33843878

• Feasibility of Centralized Electronic Patient-Reported Outcome (ePRO) Collection By an Outcome Registry, a CIBMTR Study of Patients on the Centers for Medicaid & Medicare Coverage with Evidence Development (CMS CED) Myelodysplasia Protocol Shaw, B. E., Burns, L. J., Mattila, D., Mussetter, A., Chen, M., Vasu, S., Pidala, J. A., Muffly, L., Uberti, J., Tamari, R., Leckrone, E., Myers, J., Brazauskas, R., Mau, L., Rizzo, J., Saber, W., Horowitz, M. M., Lee, S. J., Flynn, K. ELSEVIER SCIENCE INC. 2020: S66

  View details for Web of Science ID 000516887900088

• Prospective Randomized Study of Advance Directives in Allogeneic Hematopoietic Cell Transplant Recipients Muffly, L., Ramirez, Y., Burnash, S., Bisetti, E., Rezvani, A., Sundaram, V. ELSEVIER SCIENCE INC. 2020: S199

  View details for Web of Science ID 000516887900291

• Transplant Physicians' Attitudes on Candidacy for Allogeneic Hematopoietic Cell Transplantation (HCT) in Older Patients: The Need for a Standardized Geriatric Assessment (GA) Tool Mishra, A., Preussler, J. M., Al-Mansour, Z., Bachanova, V., Bhatt, V., Bredeson, C., Chhabra, S., D'Souza, A., Dahi, P. B., DeFilipp, Z., Gowda, L., Hacker, E., Hashmi, S. K., Howard, D. S., Jakubowski, A. A., Jayani, R., Johnston, L., Koll, T., Lin, R. J., McCurdy, S. R., Michaelis, L. C., Muffly, L., Nathwani, N., Olin, R. L., Popat, U. R., Rodriguez, C., Rosko, A., Runaas, L., Sabloff, M., Shore, T. B., Shune, L., Sorror, M. L., Sung, A. D., Ustun, C., Wood, W., Burns, L. J., Artz, A. S. ELSEVIER SCIENCE INC. 2020: S45–S46

  View details for Web of Science ID 000516887900060

• Clinical Actionability of Measurable Residual Disease (MRD) Assessment in the Management of Patients With Hematologic Malignancies: A Case-Based Monograph CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY Wolf, J., Fonseca, R., Muffly, L. 2020; 18 (3)

  View details for Web of Science ID 000619716900001

• Assessment of Measurable Residual Disease (MRD) in Adult Patients With Acute Lymphocytic Leukemia: Best Use and a Case Report CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY Muffly, L. 2020; 18 (3)

  View details for Web of Science ID 000619716900004

• Hepatic veno-occlusive disease in allogeneic stem cell transplant recipients with prior exposure to gemtuzumab ozogamicin or inotuzumab ozogamicin. Leukemia & lymphoma Ladha, A. n., Mannis, G. n., Muffly, L. n. 2020: 1–7

  Abstract

  Hepatic veno-occlusive disease (VOD/sinusoidal obstructive syndrome) represents a constellation of clinical findings including right upper quadrant pain, jaundice, hepatomegaly, and ascites. In the post-hematopoietic stem cell transplant (SCT) setting, the reported incidence has been 10-15%, with severe VOD historically resulting in high mortality rates. Novel agents including calicheamicin conjugated with CD33 (gemtuzumab ozogamicin; GO) and CD22 (inotuzumab ozogamicin; InO) are increasingly used for the treatment of acute myeloid leukemia and acute lymphoblastic leukemia, respectively. Both GO and InO are highly active, but also have unique hepatotoxicity profiles, including a higher risk of VOD in recipients of SCT. Introduction of GO and InO into pre-SCT leukemia management adds additional complexity to SCT patient selection and toxicity monitoring. In this article, we describe and review the risks and management associated with VOD in SCT recipients exposed to GO and InO.

  View details for DOI 10.1080/10428194.2020.1827247

  View details for PubMedID 32988266

• Calcineurin-inhibitor induced pain syndrome after stem cell transplant. Leukemia & lymphoma Varma, A. n., Loya, J. n., Junaid Hussain, M. n., Don Yun, H. n., Gobbi, E. K., Reimer, A. n., Nathan, S. n., Ustun, C. n., Muffly, L. n. 2020: 1–4

  View details for DOI 10.1080/10428194.2020.1765235

  View details for PubMedID 32431182

• Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia in Adolescents and Young Adults. JCO oncology practice Wang, A. Y., Muffly, L. S., Stock, W. n. 2020: JOP1900197

  Abstract

  Adolescents and young adults (AYAs) with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) represent a unique patient population with a disproportionate survival disadvantage compared with younger children. Substantial progress has been made as we began to understand and address the multifaceted drivers behind this outcome disparity. New insights into the biology of B-cell ALL have uncovered distinct genetic characteristics more commonly found in AYAs that affect prognosis. Dramatic improvements in survival have been achieved with the use of pediatric-inspired protocols in the front-line setting, as well as antibody-based and chimeric antigen receptor T-cell therapies in the relapsed and refractory setting. Guided by the incorporation of minimal residual disease testing to inform clinical decision making, these represent major paradigm shifts in management. Efforts to design clinical trials geared toward AYAs and to enroll AYAs in available clinical trials will ensure ongoing progress. Holistic care of AYAs with ALL further involves recognition of psychosocial issues arising as a consequence of their diagnosis and the delivery of age-appropriate supportive care.

  View details for DOI 10.1200/JOP.19.00197

  View details for PubMedID 32048928

• How I Approach the Patient Who Has MRD or Relapse After Transplant. Clinical lymphoma, myeloma & leukemia Muffly, L. n. 2020; 20 Suppl 1: S32–S33

  View details for DOI 10.1016/S2152-2650(20)30453-5

  View details for PubMedID 32862860

• Nonmyeloablative allogeneic transplantation achieves clinical and molecular remission in cutaneous T-cell lymphoma. Blood advances Weng, W. K., Arai, S. n., Rezvani, A. n., Johnston, L. n., Lowsky, R. n., Miklos, D. n., Shizuru, J. n., Muffly, L. n., Meyer, E. n., Negrin, R. S., Wang, E. n., Almazan, T. n., Million, L. n., Khodadoust, M. n., Li, S. n., Hoppe, R. T., Kim, Y. H. 2020; 4 (18): 4474–82

  Abstract

  The majority of patients with refractory, advanced-stage mycosis fungoides (MF) or Sézary syndrome (SS) have a life expectancy of <5 years. Here, we report a phase 2 study of a novel nonmyeloablative allogeneic transplantation strategy tailored for this patient population. This study has completed the enrollment, and 35 patients (13 MF, 22 SS) have undergone transplant as planned. The majority (80%) of the patients had stage IV disease and received multiple previous systemic therapies. All patients had active disease at the time of conditioning using total skin electron beam therapy, total lymphoid irradiation, and antithymocyte globulin, and received allograft infusion as outpatients. Cyclosporine or tacrolimus and mycophenolate mofetil were used for graft-versus-host disease (GVHD) prophylaxis. Patients tolerated the transplant well, with 1- and 2-year nonrelapse mortality of 3% and 14%, respectively. The day +180 cumulative incidence of grade 2 to 4 acute GVHD was 16%, and the 2-year incidence of moderate/severe chronic GVHD was 32%. With a median posttransplant follow-up of 5.4 years, the 2-, 3-, and 5-year overall survival rates were 68%, 62%, and 56%. Using high-throughput sequencing of the T-cell receptor for minimal residual disease monitoring, we observed that 43% achieved molecular remission, which was associated with a lower incidence of disease progression or relapse (9% vs 87%; P = .02). Our study also showed that patients who were aged ≥65 years at the time of allotransplant had similar clinical outcomes compared with younger patients. Thus, we have developed an alternative and potentially curative nonmyeloablative allogeneic transplant regimen for patients with advanced stage MF/SS. This trial was registered at www.clinicaltrials.gov as #NCT00896493.

  View details for DOI 10.1182/bloodadvances.2020001627

  View details for PubMedID 32941647

• Outcomes with autologous stem cell transplant vs. non-transplant therapy in patients 70 years and older with multiple myeloma. Bone marrow transplantation Lemieux, C. n., Muffly, L. S., Rezvani, A. n., Lowsky, R. n., Iberri, D. J., Craig, J. K., Frank, M. J., Johnston, L. J., Liedtke, M. n., Negrin, R. n., Weng, W. K., Meyer, E. n., Shizuru, J. n., Shiraz, P. n., Arai, S. n., Miklos, D. B., Sidana, S. n. 2020

  Abstract

  We evaluated 79 patients with multiple myeloma (MM) ≥70 years referred to our blood and marrow transplant clinic, within 1 year of diagnosis from 2010 to 2019, for consideration of autologous stem cell transplant (ASCT). Thirty-eight (48%) of 79 patients underwent ASCT. ASCT was not pursued in 41 (52%) patients due to: patient or physician preference in 80% (n = 33) or ineligibility in 20% (n = 8). Baseline characteristics of patients in the two groups were similar. Median PFS from treatment start amongst patients undergoing ASCT (n = 38) vs. not (n = 41) was 41 months vs. 33 months, p = 0.03. There was no difference in OS, with estimated 5-year OS of 73% vs. 83%, respectively (p = 0.86). Day +100 transplant-related mortality (TRM) was 0%. ASCT was an independent favorable prognostic factor for PFS in multivariate analysis, after accounting for HCT-CI score, performance status, hematologic response, and maintenance. Finally, patients ≥70 years undergoing ASCT had similar PFS compared to a contemporaneous institutional cohort of patients <70 years (n = 631) (median PFS from transplant: 36 vs. 47 months, p = 0.25). In this retrospective analysis, ASCT was associated with low TRM and better PFS in fit older adults with MM compared to non-transplant therapy, with comparable benefits as seen in younger patients.

  View details for DOI 10.1038/s41409-020-01026-7

  View details for PubMedID 32782351

• Treatment Complications and Survival Among Children and Young Adults With Acute Lymphoblastic Leukemia. JCO oncology practice Alvarez, E. M., Malogolowkin, M. n., Hoch, J. S., Li, Q. n., Brunson, A. n., Pollock, B. H., Muffly, L. n., Wun, T. n., Keegan, T. H. 2020: JOP1900572

  Abstract

  We previously demonstrated lower early mortality for young adults (YAs) with acute lymphoblastic leukemia (ALL) who received induction treatment at specialized cancer centers (SCCs) versus community hospitals. The aim of this study is to determine the impact of inpatient location of treatment throughout therapy on long-term survival, complications, and cost-associations that have not yet been evaluated at the population level.Using the California Cancer Registry linked to a hospitalization database, we identified patients, 0-39 years of age, diagnosed with first primary ALL who received inpatient treatment between 1991 and 2014. Patients were classified as receiving all or part or none of their inpatient treatment at an SCC within 3 years of diagnosis. Inverse probability-weighted, multivariable Cox regression models estimated the associations between location of treatment and sociodemographic and clinical factors with survival. We compared 3-year inpatient costs overall and per day by age group and location of care.Eighty-four percent (0-18 years; n = 4,549) of children and 36% of YAs (19-39 years; n = 683) received all treatment at SCCs. Receiving all treatment at an SCC was associated with superior leukemia-specific (hazard ratio [HR], 0.76; 95% CI, 0.67 to 0.88) and overall survival (HR, 0.87; 95% CI, 0.77 to 0.97) in children and in YAs (HR, 0.71; 95% CI, 0.61 to 0.83; HR, 0.70; 95% CI, 0.62 to 0.80) even after controlling for complications. The cost of inpatient care during the full course of therapy was higher in patients receiving all of their care at SCCs.Our results demonstrate that inpatient treatment at an SCC throughout therapy is associated with superior survival; therefore, strong consideration should be given to referring these patients to SCCs.

  View details for DOI 10.1200/JOP.19.00572

  View details for PubMedID 32525752

• CD22-Directed CAR T-Cell Therapy Induces Complete Remissions in CD19-Directed CAR-Refractory Large B-Cell Lymphoma. Blood Baird, J. H., Frank, M. J., Craig, J. n., Patel, S. n., Spiegel, J. Y., Sahaf, B. n., Oak, J. S., Younes, S. n., Ozawa, M. n., Yang, E. n., Natkunam, Y. n., Tamaresis, J. S., Ehlinger, Z. n., Reynolds, W. D., Arai, S. n., Johnston, L. n., Lowsky, R. n., Meyer, E. n., Negrin, R. S., Rezvani, A. R., Shiraz, P. n., Sidana, S. n., Weng, W. K., Davis, K. L., Ramakrishna, S. n., Schultz, L. n., Mullins, C. D., Jacob, A. P., Kirsch, I. R., Feldman, S. A., Mackall, C. L., Miklos, D. B., Muffly, L. n. 2020

  Abstract

  The prognosis for patients with large B-cell lymphoma (LBCL) progressing after treatment with chimeric antigen receptor (CAR) T-cell therapy targeting CD19 (CAR19) is poor. We report on the first three consecutive patients with autologous CAR19-refractory LBCL treated with a single infusion of autologous 1×106 CAR+ T-cells/kg targeting CD22 (CAR22) as part of a phase I dose escalation study. CAR22 therapy was relatively well tolerated, without any observed non-hematologic adverse events higher than grade 2. Following infusion, all three patients achieved complete remission, with all responses ongoing at the time of last follow up (mean 7.8 months, range 6-9.3). Circulating CAR22 cells demonstrated robust expansion (peak range 85.4-350 cells/µL), and persisted beyond three months in all patients with continued radiographic responses and corresponding decreases in circulating tumor DNA (ctDNA) beyond six months post-infusion. Further accrual at a higher dose level in this phase 1 dose-escalation study is ongoing and will explore the role of this therapy in patients who have failed prior CAR T-cell therapies. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT04088890).

  View details for DOI 10.1182/blood.2020009432

  View details for PubMedID 33512414

• Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit? Muffly, L., Curran, E. AMER SOC HEMATOLOGY. 2019: 17–23

  View details for Web of Science ID 000538564000003

• Phase I Trial Using CD19/CD22 Bispecific CAR T Cells in Pediatric and Adult Acute Lymphoblastic Leukemia (ALL) Schultz, L. M., Muffly, L. S., Spiegel, J. Y., Ramakrishna, S., Hossain, N., Baggott, C., Sahaf, B., Patel, S., Craig, J., Yoon, J., Kadapakkam, M., Majzner, R. G., Frank, M. J., Erickson, C., Marcy, A., Fujimoto, M., Bhatia, N., Meyer, E. H., Kong, K. A., Egeler, E., Mavroukakis, S., Qin, H., Fry, T. J., Feldman, S. A., Miklos, D. B., Mackall, C. L., Davis, K. L. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-129411

  View details for Web of Science ID 000518218500444

• Late Effects and Subsequent Neoplasms in Survivors of Adolescent and Young Adult Acute Lymphoblastic Leukemia: A Population-Based Analysis Including Impact of Front-Line Regimen Type Muffly, L. S., Maguire, F., Li, Q., Kennedy, V., Keegan, T. M. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-124992

  View details for Web of Science ID 000518218500312

• Improved Outcomes for Relapsed/Refractory Classic Hodgkin Lymphoma Following Autologous Stem Cell Transplantation in the Era of Novel Agents Sica, R., Spinner, M. A., Tamaresis, J. S., Advani, R. H., Johnston, L. J., Lowsky, R., Meyer, E. H., Miklos, D. B., Muffly, L. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Negrin, R. S., Arai, S. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-131532

  View details for Web of Science ID 000577160403295

• Identification of Two CAR T-Cell Populations Associated with Complete Response or Progressive Disease in Adult Lymphoma Patients Treated with Axi-Cel Good, Z., Spiegel, J. Y., Sahaf, B., Malipatlolla, M. B., Frank, M. J., Baird, J., Muffly, L. S., Claire, G. K., Craig, J., Kong, K. A., Bendall, S., Miklos, D. B., Mackall, C. L. AMER SOC HEMATOLOGY. 2019

  View details for DOI 10.1182/blood-2019-130815

  View details for Web of Science ID 000518218500765

• Central Nervous System Relapse in Adolescents and Young Adults with Acute Lymphoblastic Lymphoma Treated with Total Body Irradiation and Hematopoietic Stem Cell Transplantation Kozak, M., Yoo, C., Muffly, L., Hiniker, S. M. ELSEVIER SCIENCE INC. 2019: E472

  View details for DOI 10.1016/j.ijrobp.2019.06.1447

  View details for Web of Science ID 000485671501366

• Comparison of high doses of total body irradiation in myeloablative conditioning prior to hematopoietic cell transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Sabloff, M., Chhabra, S., Wang, T., Fretham, C., Kekre, N., Abraham, A., Adekola, K., Auletta, J. J., Barker, C., Beitinjaneh, A. M., Bredeson, C., Cahn, J., Diaz, M. A., Freytes, C., Gale, R. P., Ganguly, S., Gergis, U., Guinan, E., Hamilton, B., Hashmi, S., Hematti, P., Hildebrandt, G., Holmberg, L., Hong, S., Lazarus, H. M., Martino, R., Muffly, L., Nishihori, T., Perales, M., Yared, J., Mineishi, S., Stadtmauer, E. A., Pasquini, M. C., Loren, A. W. 2019

  Abstract

  Malignancy relapse is the most common cause of treatment failure among recipients of hematopoietic cell transplantation (HCT). Conditioning dose intensity can reduce disease relapse, but it is offset by toxicities. Improvements in radiotherapy techniques and supportive care may translate to better outcomes with higher irradiation doses in the modern era. This study compares outcomes of recipients of increasing doses of high dose total body irradiation (TBI) divided into intermediate high dose (IH 13-13.75 Gy) and high dose (HD 14 Gy) to standard dose (SD 12Gy) with cyclophosphamide (Cy). A total of 2,721 patients ages of 18 to 60 with hematologic malignancies receiving HCT from 2001 to 2013 were included. Cumulative incidence of non-relapse mortality (NRM) at 5 years was 28% (95% Cumulative Incidence [CI] 25-30%), 32% (95%CI 29-36%) and 34% (95%CI 28-39%) for SD, IH and HD, respectively (p=0.02). Patients receiving IH-TBI had a 25% higher risk of NRM compared to SD-TBI (12 Gy) (p=0.007). Corresponding cumulative incidence of relapse was 36% (95%CI 34-38%), 32% (95%CI 29-36%) and 26% (95%CI 21-31%) (p=0.001). Hazard ratio for mortality compared to SD were 1.06 (95% 0.94-1.19, p=0.36) for IH and 0.89 (95% CI 0.76-1.05, p=0.17) for HD. The study demonstrates that despite improvements in supportive care, myeloablative conditioning using higher doses of TBI (with Cy) leads to worse non-relapse mortality and offers no survival benefit over SD, despite reducing disease relapse.

  View details for DOI 10.1016/j.bbmt.2019.08.012

  View details for PubMedID 31473319

• Healthcare Utilization is High in Adult Patients Relapsing after Allogeneic Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Langston, J. A., Sundaram, V., Periyakoil, V. S., Muffly, L. 2019; 25 (8): 1659–65

  View details for DOI 10.1016/j.bbmt.2019.04.001

  View details for Web of Science ID 000483008500026

• Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Lin, J. K., Muffly, L. S., Spinner, M. A., Barnes, J. I., Owens, D. K., Goldhaber-Fiebert, J. D. 2019: JCO1802079

  Abstract

  Two anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapies are approved for diffuse large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) and tisagenlecleucel; each costs $373,000. We evaluated their cost effectiveness.We used a decision analytic Markov model informed by recent multicenter, single-arm trials to evaluate axi-cel and tisagenlecleucel in multiply relapsed/refractory, adult, diffuse large B-cell lymphoma from a US health payer perspective over a lifetime horizon. Under a range of plausible long-term effectiveness assumptions, each therapy was compared with salvage chemoimmunotherapy regimens and stem-cell transplantation. Main outcomes were undiscounted life years, discounted lifetime costs, discounted quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (3% annual discount rate). Sensitivity analyses explored uncertainty.In an optimistic scenario, assuming a 40% 5-year progression-free survival (PFS), axi-cel increased life expectancy by 8.2 years at $129,000/QALY gained (95% uncertainty interval, $90,000 to $219,000). At a 30% 5-year PFS, improvements in life expectancy were more modest (6.4 years) and expensive ($159,000/QALY gained [95% uncertainty interval, $105,000 to $284,000]). In an optimistic scenario, assuming a 35% 5-year PFS, tisagenlecleucel increased life expectancy by 4.6 years at $168,000/QALY gained (95% uncertainty interval, $105,000 to $414,000/QALY). At a 25% 5-year PFS, improvements in life expectancy were smaller (3.4 years) and more expensive ($223,000/QALY gained [95% uncertainty interval, $123,000 to $1,170,000/QALY]). Administering CAR-T to all indicated patients would increase US health care costs by approximately $10 billion over 5 years. Price reductions to $250,000 and $200,000, respectively, or payment only for initial complete response (at current prices) would allow axi-cel and tisagenlecleucel to cost less than $150,000/QALY, even at 25% PFS.At 2018 prices, it is possible that both CAR-T therapies meet a less than $150,000/QALY threshold. This depends on long-term outcomes compared with chemoimmunotherapy and stem-cell transplantation, which are uncertain. Widespread adoption would substantially increase non-Hodgkin lymphoma health care costs. Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes.

  View details for DOI 10.1200/JCO.18.02079

  View details for PubMedID 31157579

• Hematopoietic Cell Transplantation in Young Adult Acute Lymphoblastic Leukemia: A United States Population-Level Analysis JOURNAL OF ADOLESCENT AND YOUNG ADULT ONCOLOGY Muffly, L., Li, Q., Alvarez, E., Kahn, J., Winestone, L., Cress, R., Penn, D. C., Keegan, T. M. 2019; 8 (3): 254–61

  View details for DOI 10.1089/jayao.2018.0140

  View details for Web of Science ID 000473442700004

• Acute leukemia in a patient with 15q overgrowth syndrome AMERICAN JOURNAL OF MEDICAL GENETICS PART A Bodle, E. E., Gupta, R., Cherry, A. M., Muffly, L., Manning, M. A. 2019; 179 (6): 1025–29

  View details for DOI 10.1002/ajmg.a.61115

  View details for Web of Science ID 000468322800023

• Cost-effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma. Lin, J., Muffly, L. S., Spinner, M., Barnes, J. I., Owens, D. K., Goldhaber-Fiebert, J. D. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for Web of Science ID 000487345806323

• Delays in diagnosis in young patients with leukemia and lymphoma. Winestone, L., McPheeters, J., Puccetti, D., Wilkes, J., Muffly, L. S., Kahn, J., Henk, H. J., Ginsberg, J. P., Keegan, T., Pollock, B. H., Alvarez, E. AMER SOC CLINICAL ONCOLOGY. 2019

  View details for DOI 10.1200/JCO.2019.37.15_suppl.e18138

  View details for Web of Science ID 000487345802114

• Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients JCI INSIGHT Meyer, E. H., Laport, G., Xie, B. J., MacDonald, K., Heydari, K., Sahaf, B., Tang, S., Baker, J., Armstrong, R., Tate, K., Tadisco, C., Arai, S., Johnston, L., Lowsky, R., Muffly, L., Rezvani, A. R., Shizuru, J., Weng, W., Sheehan, K., Miklos, D., Negrin, R. S. 2019; 4 (10)

  View details for DOI 10.1172/jci.insight.127244

  View details for Web of Science ID 000468146300016

• EEG Findings in Chimeric Antigen Receptor T-Cell (CAR-T) Related Encephalopathy Syndrome Satyanarayan, S., Markert, M., Hovsepian, D., Post, D., Muffly, L., Miklos, D., Thomas, R., Scott, B. LIPPINCOTT WILLIAMS & WILKINS. 2019

  View details for Web of Science ID 000475965900243

• Health Care Utilization is High in Adult Patients Relapsing After Allogeneic Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Langston, J. A., Sundaram, V., Periyakoil, V. S., Muffly, L. 2019

  Abstract

  Disease relapse is the leading cause of death for patients with acute leukemia (AL) and myelodyspastic syndrome (MDS) who undergo allogeneic hematopoietic cell transplantation (HCT). Relapse post-HCT is associated with poor prognosis; however, the inpatient health care utilization of this population is unknown. Here we describe survival, intensity of health care utilization, and characteristics associated with high resource utilization at the end-of-life (EOL). Adult patients with AL/MDS who underwent HCT at a large regional referral center with subsequent relapse between 2005 and 2015 were included in this retrospective study. We compared the distribution of demographic and clinical characteristics of patients as well as health care utilization over two years post-relapse and at EOL by post-relapse disease-directed therapeutic interventions. We created a composite score for EOL healthcare utilization intensity summing the presence of any of the following criteria: death in the hospital, the use of chemotherapy, emergency department, hospitalization, intensive care unit, intubation, cardiopulmonary resuscitation, or hemodialysis in the last month of life. Higher scores indicate more intense health care use at EOL. Multivariable linear regression analysis was used to determine variables (demographic characteristics, post-relapse treatment group, advance directives documentation, palliative care referral, time to relapse) associated with EOL healthcare utilization intensity. 154 patients were included; median age at relapse was 56 years (IQR 39-63), 55% were male, 79% had AL, median time from HCT to relapse was 6 months (IQR 3-10 months). Following relapse, 28% received supportive care only, 50% received chemotherapy only, and 22% received chemotherapy plus cell therapy (either donor lymphocyte infusion (DLI), second HCT, or DLI plus second HCT). With the exception of time until relapse, baseline characteristics (gender, age, race, graft versus host disease, year of treatment) did not significantly differ by post-relapse treatment group. One hundred and thirty-six patients (88%) died within two years of relapse; survival differed significantly by post-relapse treatment group, with those receiving disease directed treatment showing lower risk of death. Health care utilization in AL/MDS patients following post-HCT relapse was high overall with 44% visiting the ED at least once (22% >= 2 times), 93% hospitalized (55% >= 2 times; 16% >= 5 times), and 38% using the ICU (median length of stay 5 days; IQR 3-10 days). Utilization was high even among those receiving only supportive care. For those patients who died, the mean (SD) intensity score for EOL healthcare use was 1.8 (1.8). Most (70%) had a marker of high-intensity healthcare utilization at the EOL or died in hospital. In multivariable analysis, post-relapse chemotherapy plus cell therapy (estimate (95% CI): 1.30 (0.35-2.26) compared to no treatment was associated with more intense EOL health care use; no other variables were associated with intensity of EOL health care use. Health care utilization following post-HCT relapse is associated with receipt of disease-directed therapy, but remains high across all groups despite known poor prognosis. Interventions are needed to minimize nonbeneficial treatments and promote goal-concordant EOL care in this seriously ill patient population.

  View details for PubMedID 30959162

• Acute leukemia in a patient with 15q overgrowth syndrome. American journal of medical genetics. Part A Bodle, E. E., Gupta, R., Cherry, A. M., Muffly, L., Manning, M. A. 2019

  Abstract

  Overgrowth syndromes are rare genetic conditions which present as global or segmental hyperplasia and are sometimes associated with increased risk of malignancy. Trisomy of the terminal portion of 15q which includes the IGFR1 gene, produces a rare overgrowth phenotype that has been termed 15q overgrowth syndrome (15q OGS). Upregulation of IGF1R has long been implicated in oncogenesis of multiple cancer types, including acute leukemias, and has been shown to render cells more susceptible to other transforming events. To date, too few cases of 15q OGS have been reported to identify any cancer predisposition. We present a case of a 34-year-old female with intellectual disability, macrocephaly, and subtle dysmorphic features who was diagnosed with mixed phenotype acute leukemia (lymphoid and myeloid). Prior to initiation of therapy she was referred to medical genetics for further evaluation and was identified as having a chromosomal translocation resulting in a partial trisomy of chromosome 15q, consistent with 15q OGS. A review of the literature for cases of malignancy in individuals with increased copy number of 15q revealed only one other reported patient. Given the small number of reported individuals, we cannot rule out an increased risk of cancer associated with this chromosomal overgrowth syndrome. Although concerns have been raised regarding treatment feasibility in the setting of chromosomal disorders, the reported patient underwent successful treatment with allogeneic hematopoietic stem-cell transplant.

  View details for PubMedID 30861314

• Decreased Early Mortality in Young Adult Patients With Acute Lymphoblastic Leukemia Treated at Specialized Cancer Centers in California. Journal of oncology practice Alvarez, E. M., Malogolowkin, M., Li, Q., Brunson, A., Pollock, B. H., Muffly, L., Wun, T., Keegan, T. H. 2019: JOP1800264

  Abstract

  PURPOSE:: Studies suggest that patients with acute lymphoblastic leukemia (ALL) have superior survival when treated at specialized cancer centers (SCCs). However, the association of early mortality (< 60 days) with location of initial care, sociodemographic factors, and complications has not been evaluated in pediatric and young adult (YA) patients with ALL.METHODS:: Using the California Cancer Registry linked to hospitalization data, we identified pediatric and YA patients with ALL who received inpatient leukemia treatment between 1991 and 2014. Patients were classified as receiving all or part/none of their care at an SCC (Children's Oncology Group- or National Cancer Institute-designated cancer center). Propensity scores were created for treatment at an SCC in each age group. Multivariable, inverse probability-weighted Cox proportional hazards regression models identified factors associated with early mortality. Results are presented as hazard ratios (HRs) and 95% CIs.RESULTS:: Among 6,531 newly diagnosed pediatric (≤ 18 years) and YA (19 to 39 years of age) patients with ALL, 1.6% of children and 5.4% of YAs died within 60 days of diagnosis. Most children received all of their care at an SCC (n = 4,752; 85.7%) compared with 35.5% of YAs (n = 1,779). Early mortality rates were lower in pediatric patients and those receiving all care at an SCC (pediatric: all, 1.5%, v part/none, 2.4%; P = .049; YAs: all, 3.2%, v part/none, 6.6%; P = .001). However, in adjusted models, receiving all care at an SCC was associated with significantly lower early mortality in YAs (HR, 0.51; 95% CI, 0.32 to 0.81), but not in pediatric patients (HR, 0.77; 95% CI, 0.47 to 1.25).CONCLUSION:: YAs with ALL experience significant reductions in early mortality after treatment at SCCs.

  View details for PubMedID 30849003

• Does Treatment Setting Matter? Evaluating Resource Utilization for Adolescents Treated in Pediatric vs Adult Cancer Institutions. Journal of the National Cancer Institute Parsons, H. M., Muffly, L., Alvarez, E. M., Keegan, T. H. 2019; 111 (3): 224–25

  View details for PubMedID 30053066

• Dose-Intense BCNU/Melphalan Regimen Followed By Autologous Hematopoietic Cell Transplantation (AHCT) Results in Prolonged PFS in Myeloma Patients Gandhi, A., Rezvani, A., Lowsky, R., Johnston, L., Shizuru, J. A., Miklos, D. B., Arai, S., Muffly, L., Meyer, E. H., Negrin, R. S., Weng, W. ELSEVIER SCIENCE INC. 2019

  View details for Web of Science ID 000540655500606

• Health Care Utilization and Intensity at End of Life is High Amongst Adults Who Relapse Following Allogeneic Hematopoietic Cell Transplantation Langston, J., Sundaram, V., Periyakoil, V., Muffly, L. ELSEVIER SCIENCE INC. 2019: 506

  View details for DOI 10.1016/j.jpainsymman.2018.12.297

  View details for Web of Science ID 000456406900300

• Assessment of older adult candidates for allogeneic hematopoietic cell transplantation: updates and remaining questions EXPERT REVIEW OF HEMATOLOGY Kennedy, V. E., Muffly, L. S. 2019; 12 (2): 99-106

  View details for DOI 10.1080/17474086.2019.1568236

  View details for Web of Science ID 000459541000003

• Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR T-cell therapy LEUKEMIA & LYMPHOMA Hossain, N. M., Dahiya, S., Le, R., Abramian, A. M., Kong, K. A., Muffly, L. S., Miklos, D. B. 2019; 60 (2): 503-506

  View details for DOI 10.1080/10428194.2018.1474463

  View details for Web of Science ID 000463555600031

• Assessment of Older Adult Candidates for Allogeneic Hematopoietic Cell Transplantation: Updates and Remaining Questions. Expert review of hematology Kennedy, V. E., Muffly, L. S. 2019

  Abstract

  INTRODUCTION: Allogeneic hematopoietic cell transplantation (allo-HCT) has seen marked growth among older adults, where chronological age is no longer a barrier to transplant. As allo-HCT expands to older and potentially less fit individuals, prognosticating transplant outcomes in this population remains an ongoing need. Areas Covered: This review summarizes pre-transplant assessment tools in optimizing patient selection and predicting transplant outcomes in older adults, including comorbidity indices, psychosocial assessment, geriatric assessment, serum biomarkers, and disease risk. This review also discusses the impact of donor age and clonal hematopoiesis of indeterminate significance on transplant outcomes. Expert Opinion: Determining which patients should be referred for transplant remains challenging, especially in older adults. Chronological age is an insufficient prognostic metric, and refining, validating, and developing novel pre-transplant risk assessment tools for geriatric patients offers great potential benefit to the field.

  View details for PubMedID 30632411

• Transplant for Acute Myeloid Leukemia in Patients Seventy Years and Older: Optimism and Opportunity. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Muffly, L. n. 2019

  View details for DOI 10.1016/j.bbmt.2019.07.024

  View details for PubMedID 31344450

• Pediatric-inspired protocols in adult acute lymphoblastic leukemia: are the results bearing fruit? Hematology. American Society of Hematology. Education Program Muffly, L. n., Curran, E. n. 2019; 2019 (1): 17–23

  Abstract

  Observational findings demonstrating improved survival for younger adults following pediatric, as opposed to adult, acute lymphoblastic leukemia (ALL) regimens have been translated into international, prospective multicenter clinical trials testing the pediatric regimen in young adult ALL. The results of these studies confirm the feasibility of delivering the pediatric regimen in the adult oncology setting and establish the superiority of this approach relative to historical adult cooperative group regimen results. Specific toxicities, including thrombosis, hepatotoxicity, and osteonecrosis, are more prevalent in adults receiving the pediatric regimen relative to young children. Persistent minimal residual disease (MRD) is a strong prognostic indicator in adults receiving the pediatric regimen; sensitive, high-quality MRD evaluation should be performed in all patients receiving these therapies. Incorporation of targeted agents, particularly in the frontline and MRD+ setting, will usher in the next era of the pediatric regimen in adult ALL.

  View details for DOI 10.1182/hematology.2019000009

  View details for PubMedID 31808881

• Impact of cytogenetic abnormalities on outcomes of adult Philadelphia-negative acute lymphoblastic leukemia after allogeneic hematopoietic stem cell transplantation: a study by the Acute Leukemia Working Committee of the Center for International Blood and Marrow Transplant Research. Haematologica Lazaryan, A. n., Dolan, M. n., Zhang, M. J., Wang, H. L., Kharfan-Dabaja, M. A., Marks, D. I., Bejanyan, N. n., Copelan, E. n., Maijhail, N. n., Waller, E. K., Chao, N. n., Prestidge, T. n., Nishihori, T. n., Kebriaei, P. n., Inamoto, Y. n., Hamilton, B. n., Hashmi, S. K., Kamble, R. T., Bacher, U. n., Hildebrandt, G. C., Stiff, P. J., McGuirk, J. n., Aldoss, I. n., Beitinjaneh, A. M., Muffly, L. n., Vij, R. n., Olsson, R. F., Byrne, M. n., Schultz, K. R., Aljurf, M. n., Seftel, M. n., Savoie, M. L., Savani, B. N., Verdonck, L. F., Cairo, M. S., Hossain, N. n., Bhatt, V. R., Frangoul, H. A., Abdel-Azim, H. n., Al Malki, M. n., Munker, R. n., Rizzieri, D. n., Khera, N. n., Nakamura, R. n., Ringdén, O. n., van der Poel, M. n., Murthy, H. S., Liu, H. n., Mori, S. n., De Oliveira, S. n., Bolaños-Meade, J. n., Elsawy, M. n., Barba, P. n., Nathan, S. n., George, B. n., Pawarode, A. n., Grunwald, M. n., Agrawal, V. n., Wang, Y. n., Assal, A. n., Castillo Caro, P. n., Kuwatsuka, Y. n., Seo, S. n., Ustun, C. n., Politikos, I. n., Lazarus, H. M., Saber, W. n., Sandmaier, B. M., de Lima, M. n., Litzow, M. n., Bachanova, V. n., Weisdorf, D. n. 2019

  Abstract

  Cytogenetic risk stratification at diagnosis has long been one of the most useful tools to assess prognosis in acute lymphoblastic leukemia. To examine the prognostic impact of cytogenetic abnormalities on outcomes after allogeneic hematopoietic cell transplantation, we studied 1731 adults with Philadelphia-negative acute lymphoblastic leukemia in complete remission who underwent myeloablative or reduced intensity/non-myeloablative conditioning transplant from unrelated or matched sibling donors reported to Center for International Blood and Marrow Transplant Research. A total of 632 patients had abnormal conventional metaphase cytogenetics. Patients with abnormal cytogenetics had 40% leukemia-free survival and 42% overall survival at 5-years post-transplant, which was similar to those with normal karyotype. Of the previously established cytogenetic risk classifications, modified Medical Research Council-Eastern Cooperative Oncology Group score was the only independent prognosticator of leukemia-free survival (p=0.03). In the multivariable analysis, monosomy 7 predicted post-transplant relapse (hazard ratio=2.11; 95% confidence interval, 1.04-4.27) and treatment failure (hazard ratio=1.97; 1.20-3.24). Complex karyotype was prognostic for relapse (hazard ratio=1.69; 1.06-2.69), whereas t(8;14) predicted treatment failure (hazard ratio=2.85; 1.35-6.02) and overall mortality (hazard ratio=3.03; 1.44-6.41). This large study suggested a novel transplant-specific cytogenetic scheme with adverse (monosomy 7, complex karyotype, del(7q), t(8;14), t(11;19), del(11q), tetraploidy/near triploidy), intermediate (normal karyotype and all other abnormalities), and favorable (high hyperdiploidy) risks to prognosticate leukemia-free survival (p=0.02). Although some previously established high-risk Philadelphia-negative cytogenetic abnormalities of acute lymphoblastic leukemia can be overcome by transplant, monosomy 7, complex karyotype, and t(8;14) continue to pose significant risks and yield inferior outcomes.

  View details for DOI 10.3324/haematol.2019.220756

  View details for PubMedID 31558669

• Nonmyeloablative TLI-ATG conditioning for allogeneic transplantation: mature follow-up from a large single-center cohort. Blood advances Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Arai, S. n., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W. K., Hoppe, R. T., Strober, S. n., Lowsky, R. n. 2019; 3 (16): 2454–64

  Abstract

  Nonmyeloablative total lymphoid irradiation and antithymocyte globulin (TLI-ATG) conditioning is protective against graft-versus-host disease (GVHD), while retaining graft-versus-tumor activity across various hematologic malignancies. We report our comprehensive experience using TLI-ATG conditioning in 612 patients with hematologic malignancies who underwent allogeneic transplantation at Stanford University from 2001 to 2016. All patients received granulocyte colony-stimulating factor-mobilized peripheral blood grafts and cyclosporine and mycophenolate mofetil for GVHD prophylaxis. The median age was 60 years (range, 21-78), with a median follow-up of 6.0 years (range, 1.0-16.4). Common diagnoses included acute myeloid leukemia (AML; n = 193), myelodysplastic syndrome (MDS; n = 94), chronic lymphocytic leukemia (CLL; n = 80), non-Hodgkin lymphoma (NHL; n = 175), and Hodgkin lymphoma (HL; n = 35). Thirty-four percent of patients had a comorbidity index ≥3, 30% had a high to very high disease risk index, and 56% received unrelated donor grafts, including 15% with HLA-mismatched donors. Ninety-eight percent underwent transplant in the outpatient setting, and 57% were never hospitalized from days 0 through 100. The 1-year rates of nonrelapse mortality (NRM), grade II-IV acute GVHD, and extensive chronic GVHD were 9%, 14%, and 22%, respectively. The 4-year estimates for overall and progression-free survival were 42% and 32% for AML, 30% and 21% for MDS, 67% and 43% for CLL, 68% and 45% for NHL, and 78% and 49% for HL. Mixed chimerism correlated with the risk of relapse. TLI-ATG conditioning was well tolerated, with low rates of GVHD and NRM. Durable remissions were observed across hematologic malignancies, with particularly favorable outcomes for heavily pretreated lymphomas. Several efforts are underway to augment donor chimerism and reduce relapse rates while maintaining the favorable safety and tolerability profile of this regimen.

  View details for DOI 10.1182/bloodadvances.2019000297

  View details for PubMedID 31427277

• Central Nervous System Relapse After Stem Cell Transplantation in Adolescents and Young Adults with Acute Lymphoblastic Leukemia: A Single-Institution Experience. Journal of adolescent and young adult oncology Kozak, M. M., Yoo, C. H., Gutkin, P. M., von Eyben, R. n., Agarwal, R. n., Donaldson, S. S., Muffly, L. n., Hiniker, S. M. 2019

  Abstract

  Purpose: To evaluate outcomes and central nervous system (CNS) relapse in adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL), who underwent total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (allo-SCT). Methods: A total of 136 AYA patients with ALL who received TBI before allo-SCT between 1998 and 2018 were reviewed. Twenty patients received cranial radiation in their initial treatment before conditioning for transplant and were excluded. Competing risk analysis was used to estimate the cumulative incidence of relapse. Kaplan-Meier and log-rank tests were used to calculate overall survival (OS) and to identify factors predictive of relapse. OS and time to relapse were calculated from date of allo-SCT. Results: One hundred sixteen patients were included in the analysis. Median age was 27 years and median follow-up time was 42 months. Twenty-six patients suffered a disease relapse and 49 died, 26 of posttransplantation complications. The median time to relapse was 7 months and the 5-year OS was 60%. Seven patients had a CNS relapse: 4 of 20 patients (25%) with pre-SCT CNS disease had a post-allo-SCT CNS relapse compared to 3 of 97 (3.1%) without pre-SCT CNS disease. Median time to CNS relapse was 7 months. Patients with post-SCT CNS relapse had median OS of 19 months. Conclusions: AYA patients with CNS disease who undergo an allo-SCT have a high rate of CNS relapse. The addition of additional CNS-directed therapy to transplant protocols warrants further investigation.

  View details for DOI 10.1089/jayao.2019.0121

  View details for PubMedID 31747341

• Cost Effectiveness of Chimeric Antigen Receptor T-Cell Therapy in Multiply Relapsed or Refractory Adult Large B-Cell Lymphoma Journal of Clinical Oncology Lin, J. K., Muffly, L. S., Spinner, M. A., Barnes, J. I., Owens, D. K., Goldhaber-Fiebert, J. D. 2019

  View details for DOI 10.1200/JCO.18.02079

• Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients. JCI insight Meyer, E. H., Laport, G. n., Xie, B. J., MacDonald, K. n., Heydari, K. n., Sahaf, B. n., Tang, S. W., Baker, J. n., Armstrong, R. n., Tate, K. n., Tadisco, C. n., Arai, S. n., Johnston, L. n., Lowsky, R. n., Muffly, L. n., Rezvani, A. R., Shizuru, J. n., Weng, W. K., Sheehan, K. n., Miklos, D. n., Negrin, R. S. 2019; 4 (10)

  Abstract

  BACKGROUNDIn preclinical murine and early clinical studies of hematopoietic cell transplantation, engineering of donor grafts with defined ratios of CD4+CD25+FoxP3+ Tregs to conventional T cells (Tcons) results in the prevention of graft-versus-host disease and improved immune reconstitution. The use of highly purified primary graft Tregs for direct cell infusion has potential advantages over impure immunomagnetic selection or culture expansion, but has not been tested clinically. We performed a phase I study of the timed addition of CD34-selected hematopoietic stem cells and Tregs, followed by Tcons for the treatment of patients with high-risk hematological malignancies.METHODSWe present interim evaluation of a single-center open phase I/II study of administration of human leukocyte-matched Tregs and CD34-selected hematopoietic cells, followed by infusion of an equal ratio of Tcons in adult patients undergoing myeloablative hematopoietic stem cell transplantation (HCT) for high-risk or active hematological malignancies. Tregs were purified by immunomagnetic selection and high-speed cell sorting.RESULTSHere we report results for the first 12 patients who received Tregs of between 91% and 96% purity. Greater than grade II GVHD was noted in 2 patients in the first cohort of 5 patients, who received cryopreserved Tregs, but neither acute nor chronic GVHD was noted in the second cohort of 7 patients, who received fresh Tregs and single-agent GVHD prophylaxis. Patients in the second cohort appeared to have normal immune reconstitution compared with patients who underwent transplantation and did not develop GVHD.CONCLUSIONOur study shows that the use of highly purified fresh Tregs is clinically feasible and supports continued investigation of the strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT01660607.FUNDINGNIH NHBLI R01 HL114591 and K08HL119590.

  View details for PubMedID 31092732

• Disparities in Cancer-Related Mortality and Long-Term Survival in Adolescent and Young Adults with Hodgkin Lymphoma: A Population-Level Analysis across the United States Kahn, J. M., Keegan, T. M., Alvarez, E., Muffly, L. S., Parsons, H., Winestone, L. E., Bleyer, A. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-119382

  View details for Web of Science ID 000454842805146

• Impact of Myeloablative Total Body Irradiation Versus Chemotherapy on Late Effects and Survival Among Adolescent and Young Adult Survivors of Hematopoietic Cell Transplantation for Acute Leukemia: A Center for International Blood and Marrow Transplant Research (CIBMTR) Analysis Lee, C. J., Kim, S., Tecca, H. R., Brazauskas, R., Battiwalla, M., Buchbinder, D. K., Flowers, M. D., Phelan, R., Shaw, B. E., Muffly, L. S. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-113031

  View details for Web of Science ID 000454837600306

• Medical Conditions Among Survivors of Adolescent and Young Adult Non-Hodgkin Lymphoma (NHL), Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML) Keegan, T. M., Muffly, L. S., Li, Q., Alvarez, E., Brunson, A. M., Malogolowkin, M., Wun, T. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-111553

  View details for Web of Science ID 000454837602217

• Hematopoietic Cell Transplantation in First Remission Amongst Adolescent and Young Adult Acute Lymphoblastic Leukemia: A Population-Level Analysis across the United States Muffly, L. S., Li, Q., Alvarez, E., Kahn, J. M., Winestone, L. E., Cress, R., Penn, D., Keegan, T. M. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-111205

  View details for Web of Science ID 000454842803001

• Nonmyeloablative Allogeneic Transplantation Using TLI-ATG Conditioning for Lymphoid and Myeloid Malignancies: Mature Follow-up from a Large, Single Institution Cohort Spinner, M. A., Kennedy, V. E., Tamaresis, J. S., Lavori, P. W., Elder, L. V., Arai, S., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Hoppe, R. T., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-113597

  View details for Web of Science ID 000454842804265

• 1 Study of CD19/CD22 Bispecific Chimeric Antigen Receptor (CAR) Therapy in Children and Young Adults with B Cell Acute Lymphoblastic Leukemia (ALL) Schultz, L. M., Davis, K. L., Baggott, C., Chaudry, C., Marcy, A., Mavroukakis, S., Sahaf, B., Kong, K. A., Muffly, L. S., Kim, S., Meyer, E. H., Fry, T. J., Qin, H., Miklos, D. B., Mackall, C. L. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-117445

  View details for Web of Science ID 000454837602274

• Phase I Experience with a Bi-Specific CAR Targeting CD19 and CD22 in Adults with B-Cell Malignancies Hossain, N., Sahaf, B., Abramian, M., Spiegel, J. Y., Kong, K., Kim, S., Mavroukakis, S., Oak, J., Natkunam, Y., Meyer, E. H., Frank, M. J., Feldman, S. A., Long, S. R., Qin, H., Fry, T. J., Muffly, L. S., Mackall, C. L., Miklos, D. B. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-110142

  View details for Web of Science ID 000454837601199

• Elevated Axicabtagene Ciloleucel (CAR-19) Expansion By Immunophenotyping Is Associated with Toxicity in Diffuse Large B-Cell Lymphoma Spiegel, J. Y., Sahaf, B., Hossain, N., Frank, M. J., Claire, G., Abramian, M., Latchford, T., Villa, B., Cancilla, J., Oak, J., Natkunam, Y., Long, S. R., Arai, S., Johnston, L. J., Lowsky, R., Meyer, E. H., Muffly, L. S., Negrin, R. S., Rezvani, A. R., Shizuru, J. A., Weng, W., Kong, K. A., Mackall, C. L., Miklos, D. B. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-113261

  View details for Web of Science ID 000454837601285

• Health Care Utilization Is High Amongst Adults Who Relapse Following Allogeneic Hematopoietic Cell Transplantation Langston, J., Sundaram, V., Periyakoil, V., Muffly, L. S. AMER SOC HEMATOLOGY. 2018

  View details for DOI 10.1182/blood-2018-99-113633

  View details for Web of Science ID 000454842805058

• Another reason to encourage psychosocial risk assessment in hematopoietic cell transplantation BONE MARROW TRANSPLANTATION Muffly, L., Artz, A. 2018; 53 (11): 1416-1417

  View details for DOI 10.1038/s41409-018-0143-3

  View details for Web of Science ID 000451621400006

• End-of-Life Care Intensity in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: A Population-Level Analysis JOURNAL OF CLINICAL ONCOLOGY Johnston, E. E., Muffly, L., Alvarez, E., Saynina, O., Sanders, L. M., Bhatia, S., Chamberlain, L. J. 2018; 36 (30)

  View details for DOI 10.1200/JCO.2018.78.0957

  View details for Web of Science ID 000447725000008

• Care at specialized cancer centers among young adults with acute lymphoblastic leukemia in California. Leukemia & lymphoma Alvarez, E., Muffly, L., Li, Q., Brunson, A., Wun, T., Chamberlain, L., Keegan, T. 2018; 59 (10): 2482–84

  View details for PubMedID 29424251

• Treatment of young adults with Philadelphia-negative acute lymphoblastic leukemia and lymphoblastic lymphoma: Hyper-CVAD vs. pediatric-inspired regimens AMERICAN JOURNAL OF HEMATOLOGY Siegel, S. E., Advani, A., Seibel, N., Muffly, L., Stock, W., Luger, S., Shah, B., DeAngelo, D. J., Freyer, D. R., Douer, D., Johnson, R. H., Hayes-Lattin, B., Lewis, M., Jaboin, J. J., Coccia, P. F., Bleyer, A. 2018; 93 (10): 1254–66

  Abstract

  For young adults with acute lymphoblastic leukemia, pediatric-based regimens are likely to provide the following when compared to hyper-CVAD regimens: better disease control, less hospitalization time, diminished acute toxicities, decreased financial cost, more quality-adjusted life years, and fewer adverse late effects, such as infertility, myelodysplasia, and second malignant neoplasms. There are also reasons to expect less cardiac and cognitive dysfunction after pediatric regimens. The improved quality and quantity of life associated with pediatric regimens renders them preferable to hyper-CVAD regimens for the treatment of Philadelphia-negative B-precursor or T-cell acute lymphoblastic leukemia and lymphoblastic lymphoma in young adults.

  View details for PubMedID 30058716

• A Three-Step Letter Advance Directive Procedure to Facilitate Patient-Proxy Alignment in Advance Care Planning JOURNAL OF PALLIATIVE MEDICINE Alagappan, M., Richardson, M. T., Schoen, M. K., Muffly, L., Tierney, K., Jenkins, P., Neri, E., Kraemer, H. C., Periyakoil, V. S. 2018

  Abstract

  Little is known about the extent of alignment between hematopoietic stem cell transplant (HSCT) patients and their healthcare proxies with respect to advance care planning (ACP).To determine if a structured three-step process using the letter advance directive (LAD) could (1) allow for the differences in opinion between patient-proxy dyads to surface and (2) help bridge preexisting discordance about specific treatment choices.Blinded to each other, the HSCT patient (LAD-1) and proxy (LAD-2) each completed the LAD (step 1). They unmasked, compared LAD-1 and LAD-2, and discussed their choices (step 2). They completed a final letter directive (LAD-3) by consensus (step 3). Settings/Participants: Convenience sample of eighty dyads (patient and proxy) at a regional HSCT referral center.The mean patient-proxy concordance was 72.9% for the 12 questions in the LAD. Wanting to be pain free at the end of life was the statement with the most amount of agreement (88.75% in LAD-1, 91.25% in LAD-2, and 90% in LAD-3). Patient-proxy dyads had notable discordance related to specific treatments. The highest discordance was related to ventilator support (46.3% of patients refused it, while 58.8% of proxies refused on behalf of the patient). Overall, proxies were more likely than patients to opt in for dialyses and hospice care but more likely to opt out for cardiac resuscitation and sedation to palliate refractory symptoms. On open discussion, patient-proxy discordance mostly resolved in favor of the patient.The ACP process should allow for patient-proxy differences to surface, facilitate a discussion about the granular details with the goal of reaching consensus. Our three-step approach using the LAD is an effective way to identify areas of patient-proxy concordance and discordance about specific treatment preferences. A structured patient-proxy discussion using the LAD helped reconcile discordance and most often in favor of a patient's original wishes.

  View details for PubMedID 30247088

• End-of-Life Care Intensity in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation: A Population-Level Analysis. Journal of clinical oncology : official journal of the American Society of Clinical Oncology Johnston, E. E., Muffly, L., Alvarez, E., Saynina, O., Sanders, L. M., Bhatia, S., Chamberlain, L. J. 2018: JCO2018780957

  Abstract

  Purpose Intensity of end-of-life care receives much attention in oncology because of concerns that high-intensity care is inconsistent with patient goals, leads to worse caregiver outcomes, and is expensive. Little is known about such care in those undergoing allogeneic hematopoietic cell transplantation (HCT), a population at high risk for morbidity and mortality. Patients and Methods We conducted a population-based analysis of patients who died between 2000 and 2013, within 1 year of undergoing an inpatient allogeneic HCT using California administrative data. Previously validated markers of intensity were examined and included: hospital death, intensive care unit (ICU) admission, and procedures such as intubation and cardiopulmonary resuscitation at end of life. Multivariable logistic regression models determined clinical and sociodemographic factors associated with: hospital death, a medically intense intervention (ICU admission, cardiopulmonary resuscitation, hemodialysis, intubation), and ≥ two intensity markers. Results Of the 2,135 patients in the study population, 377 were pediatric patients (age ≤ 21 years), 461 were young adults (age 22 to 39 years), and 1,297 were adults (age ≥ 40 years). The most common intensity markers were: hospital death (83%), ICU admission (49%), and intubation (45%). Medical intensity varied according to age, underlying diagnosis, and presence of comorbidities at time of HCT. Patients with higher-intensity end-of-life care included patients age 15 to 21 years and 30 to 59 years, patients with acute lymphoblastic leukemia, and those with comorbidities at time of HCT. Conclusion Patients dying within 1 year of inpatient allogeneic HCT are receiving medically intense end-of-life care with variations related to age, underlying diagnosis, and presence of comorbidities at time of HCT. Future studies need to determine if these patterns are consistent with patient and family goals.

  View details for PubMedID 30183467

• Detection of Measurable Residual Disease by Next-Generation Sequencing in Paired Blood and Bone Marrow Samples from Patients with Lymphoid Malignancies Miklos, D., Muffly, L., Lee, L., Crossley, B. CIG MEDIA GROUP, LP. 2018: S295–S296

  View details for Web of Science ID 000444343400290

• Minimal Residual Disease Monitoring of Acute Lymphoblastic Leukemia by High-Throughput Sequencing of the Peripheral Blood: Case Examples and Literature Review Muffly, L. CIG MEDIA GROUP, LP. 2018: S53–S55

  View details for Web of Science ID 000444343400024

• Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR T-cell therapy. Leukemia & lymphoma Hossain, N. M., Dahiya, S., Le, R., Abramian, A. M., Kong, K. A., Muffly, L. S., Miklos, D. B. 2018: 1–4

  View details for PubMedID 29966461

• Improved survival among children and adolescent and young adults with acute lymphoblastic leukemia (ALL) treated at specialized cancer centers in California. Alvarez, E., Malogolowkin, M. H., Li, Q., Muffly, L. S., Wun, T., Keegan, T. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.15_suppl.10502

  View details for Web of Science ID 000442916003491

• Advance Directive Utilization Is Associated with Less Aggressive End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Cappell, K., Sundaram, V., Park, A., Shiraz, P., Gupta, R., Jenkins, P., Periyakoil, V. J., Muffly, L. 2018; 24 (5): 1035–40

  View details for DOI 10.1016/j.bbmt.2018.01.014

  View details for Web of Science ID 000433400000021

• Decreased Early Mortality Associated With the Treatment of Acute Myeloid Leukemia at National Cancer Institute-Designated Cancer Centers in California CANCER Ho, G., Wun, T., Muffly, L., Li, Q., Brunson, A., Rosenberg, A. S., Jonas, B. A., Keegan, T. M. 2018; 124 (9): 1938–45

  Abstract

  To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML).Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis).Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs.The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society.

  View details for PubMedID 29451695

• Pediatric-Inspired Treatment Regimens for Adolescents and Young Adults With Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia A Review JAMA ONCOLOGY Siegel, S. E., Stock, W., Johnson, R. H., Advani, A., Muffly, L., Douer, D., Reed, D., Lewis, M., Freyer, D. R., Shah, B., Luger, S., Hayes-Lattin, B., Jaboin, J. J., Coccia, P. F., DeAngelo, D. J., Seibel, N., Bleyer, A. 2018; 4 (5): 725–34

  Abstract

  The incidence of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in adolescent and young adult (AYA) patients (age range, 15-39 years) in the United States is increasing at a greater rate than in younger or older persons. Their optimal treatment has been increasingly debated as pediatric regimens have become more widely used in the age group. This review compares the basic features of pediatric and adult chemotherapy regimens for ALL and LBL, recognizes and describes the challenges of the pediatric regimen, and suggests strategies to facilitate its adoption for AYAs with ALL and LBL.All but 2 of 25 published comparisons of outcomes with pediatric and adult regimens for ALL and LBL in AYAs and 1 meta-analysis favor the pediatric regimen. After more than a half-century of clinical trials of the pediatric regimens, including at least 160 phase 3 trials in the United States, the pediatric regimens have become far more complex than most adult regimens. Asparaginase, a critical component of the pediatric regimens, is more difficult to administer to AYAs (and older patients) but nonetheless has a favorable benefit to toxicity ratio for AYAs. A dramatic reduction in outcome of ALL and LBL during the AYA years (the "survival cliff") is coincident with similar reductions in proportions of AYAs referred to academic centers and enrolled on clinical trials (the "accrual cliff" and "referral cliff").The accumulating data increasingly support treating AYAs with ALL and LBL with a pediatric-inspired regimen or an approved institutional or national clinical trial tailored for this patient group. A need to develop clinical trials specifically for AYAs and to encourage their participation is paramount, with a goal to improve both the quantity and quality of survival.

  View details for PubMedID 29450465

• Another reason to encourage psychosocial risk assessment in hematopoietic cell transplantation. Bone marrow transplantation Muffly, L., Artz, A. 2018

  View details for PubMedID 29588499

• Infusion of donor-derived CD8(+) memory T cells for relapse following allogeneic hematopoietic cell transplantation BLOOD ADVANCES Muffly, L., Sheehan, K., Armstrong, R., Jensen, K., Tate, K., Rezvani, A. R., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Meyer, E., Weng, W., Laport, G. G., Negrin, R. S., Strober, S., Lowsky, R. 2018; 2 (6): 681–90

  Abstract

  Murine models showed that CD8+CD44hi memory T (TM) cells could eradicate malignant cells without inducing graft-versus-host disease (GVHD). We evaluated the feasibility and safety of infusing freshly isolated and purified donor-derived phenotypic CD8+ TM cells into adults with disease relapse after allogeneic hematopoietic cell transplantation (HCT). Phenotypic CD8 TM cells were isolated after unmobilized donor apheresis using a tandem immunomagnetic selection strategy of CD45RA depletion followed by CD8+ enrichment. Fifteen patients received CD8+ TM cells at escalating doses (1 × 106, 5 × 106, or 10 × 106 cells per kg). Thirteen received cytoreduction before CD8+ TM cell infusion, and 9 had active disease at the time of infusion. Mean yield and purity of the CD8+ TM infusion were 38.1% and 92.8%, respectively; >90% had CD8+ T effector memory phenotype, cytokine expression, and secretion profile. No adverse infusional events or dose-limiting toxicities occurred; GVHD developed in 1 patient (grade 2 liver). Ten patients (67%) maintained or achieved response (7 complete response, 1 partial response, 2 stable disease) for at least 3 months after infusion; 4 of the responders had active disease at the time of infusion. With a median follow-up from infusion of 328 days (range, 118-1328 days), median event-free survival and overall survival were 4.9 months (95% confidence interval [CI], 1-19.3 months) and 19.6 months (95% CI, 5.6 months to not reached), respectively. Collection and enrichment of phenotypic CD8+ TM cells is feasible, well tolerated, and associated with a low incidence of GVHD when administered as a manipulated infusion of donor lymphocytes in patients who have relapsed after HCT. This trial was registered at www.clinicaltrials.gov as #NCT01523223.

  View details for PubMedID 29572391

• Phase I/II Trial for Patients with Advanced Hematologic Malignancies Undergoing Myeloablative Allogeneic HCT with a T Cell Depleted Graft with Infusion of Conventional T Cells and Regulatory T Cells Meyer, E., Laport, G. G., Tantsura, I., Tang, S., Sahaf, B., Rangarajan, K., Armstrong, R., Tate, K., Tudisco, C., Sheehan, K., Arai, S., Johnston, L., Muffly, L., Lowsky, R., Rezvani, A., Weng, W., Miklos, D., Negrin, R. S. ELSEVIER SCIENCE INC. 2018: S145

  View details for Web of Science ID 000425476000186

• Management of Acute Lymphoblastic Leukemia in Young Adults CLINICAL ADVANCES IN HEMATOLOGY & ONCOLOGY Muffly, L., Reizine, N., Stock, W. 2018; 16 (2): 138–46

  Abstract

  Substantial interest in acute lymphoblastic leukemia (ALL) in young adults (YAs) and investigations focused on this patient population have resulted in therapeutic advancements that are changing the management paradigm and improving outcomes. The pediatric ALL approach is feasible and effective when administered by medical oncologists. Advanced diagnostics and minimal residual disease measurements aid in prognostication and have resulted in shifting recommendations regarding allogeneic hematopoietic cell transplant in first remission. Blinatumomab, inotuzumab, and chimeric antigen receptor T-cell therapies are transforming the treatment of relapsed/refractory ALL. This comprehensive review of the current management of ALL in YAs summarizes recent scientific developments and clinical trial findings related to ALL biology, frontline management approaches, novel therapies, and supportive care specific to this patient population. Finally, a practical guide to modern YA management for practicing clinicians is provided.

  View details for PubMedID 29741514

• Advance Directive Utilization is Associated with Less Aggressive End-of-Life Care in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation Cappell, K. n., Sundaram, V. n., Park, A. n., Shiraz, P. n., Gupta, R. n., Jenkins, P. n., Periyakoil, V. S., Muffly, L. n. 2018

  Abstract

  Background Allogeneic hematopoietic cell transplantation (HCT) is associated with significant morbidity and mortality, making advance care planning (ACP) and management especially important in this patient population. A paucity of data exists on the utilization of ACP amongst allogeneic HCT recipients, and the relationship between ACP and intensity of health care utilization in these patients. Methods We performed a retrospective review of patients receiving allogeneic HCT at our institution from 2008 to 2015 who had subsequently died following HCT. Documentation and timing of advance directive (AD) completion were abstracted from the electronic medical record. Outcomes of interest included (a) utilization of intensive care unit level of care (ICU) at (i) any time point following HCT, (ii) within 30 days of death, (iii) within 14 days of death, (b) use of mechanical ventilation at any time point following HCT, and (c) location of death. Univariate logistic regression was performed to explore associations between AD completion and each outcome. Results Of the 1031 patients who received allogeneic HCT during the study period, there were 422 (41%) decedents who are included in the analysis. Forty-four percent had AD documentation prior to death. A majority of patients (69%) indicated that if terminally ill, they did not wish to be subjected to life-prolonging treatment attempts. Race/ethnicity was significantly associated with AD documentation, with Non-Hispanic White patients documenting ADs more frequently (51%) compared to Hispanic (22%) or Asian patients (35%); p= 0.0007. Patients with AD were less likely to utilize the ICU during the transplant course (41% for patients with AD versus 52% of patients without AD; p= 0.03) and also were less likely to receive mechanical ventilation at any point following transplantation (21% versus 37%; p<0.001). AD documentation was also associated with decreased ICU utilization at the end-of-life; relative to patients without AD, patients with AD were more likely to die at home or in hospital as opposed to in the ICU (OR 0.44, 95% CI 0.27-0.72).ACP remains underutilized in allogeneic HCT. Adoption of a systematic practice to standardize AD documentation as part of allogeneic HCT planning has the potential to significantly reduce ICU utilization and mechanical ventilation while improving quality of care at end-of-life in HCT recipients.

  View details for PubMedID 29371107

• Inotuzumab ozogamicin: a CD22 mAb-drug conjugate for adult relapsed or refractory B-cell precursor acute lymphoblastic leukemia DRUG DESIGN DEVELOPMENT AND THERAPY Yurkiewicz, I. R., Muffly, L., Liedtke, M. 2018; 12: 2293–2300

  Abstract

  Despite improved rates of remission and cure in newly diagnosed adult acute lymphoblastic leukemia (ALL), the prognosis for patients with relapsed or refractory disease remains poor and the 5-year overall survival rate after relapse is under 10%. A recent paradigm shift has focused on the promise of targeted immunotherapy rather than standard chemotherapy, as ALL blast cells express a variety of antigens, and monoclonal antibodies may be developed to identify and destroy the leukemic cells. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin. CD22 expression is detected on leukemic blasts in over 90% of patients with ALL. Based on promising results from preclinical studies, inotuzumab ozogamicin was tested in Phase 1/2 and Phase 3 clinical trials and it demonstrated improved complete remission rates, progression-free survival and overall survival in relapsed or refractory adult ALL compared to standard therapy. Ongoing studies are evaluating the value of inotuzumab ozogamicin when given in combination with chemotherapy as part of upfront treatment. This review discusses the drug's biochemical properties and mechanism of action, preclinical research outcomes, clinical trial results, adverse events and toxicities, drug approval and ongoing investigations.

  View details for PubMedID 30087554

• Allogeneic transplantation using TLI-ATG conditioning for Hodgkin lymphoma after failure of autologous transplantation. Blood advances Spinner, M. A., Advani, R. H., Hoppe, R. T., Lowsky, R. n., Muffly, L. S. 2018; 2 (13): 1547–50

  View details for PubMedID 29970391

• Care at specialized cancer centers among young adults with acute lymphoblastic leukemia in California LEUKEMIA & LYMPHOMA Alvarez, E., Muffly, L., Li, Q., Brunson, A., Wun, T., Chamberlain, L., Keegan, T. 2018; 59 (10): 2482-2484

  View details for DOI 10.1080/10428194.2018.1427856

  View details for Web of Science ID 000455166400029

• Validation of the Hematopoietic Cell Transplantation-Specific Comorbidity Index in Nonmyeloablative Allogeneic Stem Cell Transplantation BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Veeraputhiran, M., Yang, L., Sundaram, V., Arai, S., Lowsky, R., Miklos, D., Meyer, E., Muffly, L., Negrin, R., Rezvani, A., Shizuru, J., Weng, W., Johnston, L. 2017; 23 (10): 1744–48

  Abstract

  The Hematopoietic Cell Transplantation (HCT)-Specific Comorbidity Index (HCT-CI) has been extensively studied in myeloablative and reduced-intensity conditioning regimens, with less data available regarding the validity of HCT-CI in nonmyeloablative (NMA) allogeneic transplantation. We conducted a retrospective analysis to evaluate the association between HCT-CI and nonrelapse mortality (NRM) and all-cause mortality (ACM) in patients receiving the total lymphoid irradiation and antithymocyte globulin (TLI/ATG) NMA transplantation preparative regimen. We abstracted demographic and clinical data from consecutive patients, who received allogeneic HCT with the TLI/ATG regimen between January 2008 and September 2014, from the Stanford blood and marrow transplantation database. We conducted univariable and multivariable Cox proportional hazards regression models to evaluate the association between HCT-CI and NRM and ACM. In all, 287 patients were included for analysis. The median age of the patients was 61 (range, 22 to 77) years. The median overall survival was 844 (range, 374 to 1484) days. Most patients had Karnofsky performance score of 90 or above (85%). Fifty-two (18%) patients relapsed within 3 months and 108 (38%) patients relapsed within 1 year, with a median time to relapse of 163 (range, 83 to 366) days. Among the comorbidities in the HCT-CI identified at the time of HCT, reduced pulmonary function was the most common (n = 89), followed by prior history of malignancy (n = 39), psychiatric condition (n = 38), and diabetes (n = 31). Patients with higher HCT-CI scores had higher mortality risks for ACM (hazard ratio [HR], 1.95; 95% confidence interval [CI], 1.22 to 3.14 for HCT-CI score 1 or 2 and HR, 1.85; 95% CI, 1.11 to 3.08 for HCT-CI score ≥ 3, compared with 0, respectively). Among individual HCT-CI variables, diabetes (HR, 2.31; 95% CI, 1.79 to 2.89; P = .003) and prior solid tumors (HR, 1.75; 95% CI, 1.02 to 3.00; P = .043) were associated with a higher risk of ACM. Higher HCT-CI scores were significantly associated with higher risk of death. HCT-CI is a valid tool for predicting ACM in NMA TLI/ATG allogeneic HCT.

  View details for PubMedID 28668491

• Increasing use of allogeneic hematopoietic cell transplantation in patients aged 70 years and older in the United States BLOOD Muffly, L., Pasquini, M. C., Martens, M., Brazauskas, R., Zhu, X., Adekola, K., Aljurf, M., Ballen, K. K., Bajel, A., Baron, F., Battiwalla, M., Beitinjaneh, A., Cahn, J., Carabasi, M., Chen, Y., Chhabra, S., Ciurea, S., Copelan, E., D'Souza, A., Edwards, J., Foran, J., Freytes, C. O., Fung, H. C., Gale, R., Giralt, S., Hashmi, S. K., Hildebrandt, G. C., Ho, V., Jakubowski, A., Lazarus, H., Luskin, M. R., Martino, R., Maziarz, R., McCarthy, P., Nishihori, T., Olin, R., Olsson, R. F., Pawarode, A., Peres, E., Rezvani, A. R., Rizzieri, D., Savani, B. N., Schouten, H. C., Sabloff, M., Seftel, M., Seo, S., Sorror, M. L., Szer, J., Wirk, B. M., Wood, W. A., Artz, A. 2017; 130 (9): 1156–64

  Abstract

  In this study, we evaluated trends and outcomes of allogeneic hematopoietic cell transplantation (HCT) in adults ≥70 years with hematologic malignancies across the United States. Adults ≥70 years with a hematologic malignancy undergoing first allogeneic HCT in the United States between 2000 and 2013 and reported to the Center for International Blood and Marrow Transplant Research were eligible. Transplant utilization and transplant outcomes, including overall survival (OS), progression-free survival (PFS), and transplant-related mortality (TRM) were studied. One thousand one hundred and six patients ≥70 years underwent HCT across 103 transplant centers. The number and proportion of allografts performed in this population rose markedly over the past decade, accounting for 0.1% of transplants in 2000 to 3.85% (N = 298) in 2013. Acute myeloid leukemia and myelodysplastic syndromes represented the most common disease indications. Two-year OS and PFS significantly improved over time (OS: 26% [95% confidence interval (CI), 21% to 33%] in 2000-2007 to 39% [95% CI, 35% to 42%] in 2008-2013, P < .001; PFS: 22% [16% to 28%] in 2000-2007 to 32% [95% CI, 29% to 36%] in 2008-2013, P = .003). Two-year TRM ranged from 33% to 35% and was unchanged over time (P = .54). Multivariable analysis of OS in the modern era of 2008-2013 revealed higher comorbidity by HCT comorbidity index ≥3 (hazard ratio [HR], 1.27; P = .006), umbilical cord blood graft (HR, 1.97; P = .0002), and myeloablative conditioning (HR, 1.61; P = .0002) as adverse factors. Over the past decade, utilization and survival after allogeneic transplant have increased in patients ≥70 years. Select adults ≥70 years with hematologic malignancies should be considered for transplant.

  View details for PubMedID 28674027

• Coordination of Care in Survivorship After Treatment of Hematological Malignancies-The Journey is Not Over Yet. Current hematologic malignancy reports Lee, C. J., Muffly, L. S. 2017

  Abstract

  The number of adult survivors of hematologic malignancies is steadily growing. This population is at moderate to high risk for cancer survivorship issues including physical and psychosocial sequelae of intensive cancer therapies. Although cancer survivorship is a growing field in pediatric and solid tumor oncology, survivorship care and research has often been overlooked in the hematologic malignancies. In this review, we focus specifically on survivorship issues related to adult patients with hematologic malignancies and provide commentary on the role of cancer survivorship, proposed survivorship care models, and the economic and health policy obstacles associated with moving the cancer survivorship field forward in this very important patient population.

  View details for DOI 10.1007/s11899-017-0390-1

  View details for PubMedID 28534144

• Circulating tumor DNA assessment in patients with diffuse large B-cell lymphoma following CAR-T therapy. Dahiya, S., Le, R., Hossain, N., Abramian, M., Muffly, L. S., Miklos, D. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for DOI 10.1200/JCO.2017.35.15_suppl.7552

  View details for Web of Science ID 000411932200007

• Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Leukemia & lymphoma Lee, C. J., Shiraz, P., Muffly, L. 2017; 58 (3): 516-527

  Abstract

  The use of pharmacologic agents to maintain remission following allogeneic hematopoietic cell transplantation (HCT) is a topic of increasing interest and exploration for patients with high-risk acute myeloid leukemia (AML). This review details published and ongoing studies focused on post-transplant pharmacologic maintenance for AML. While early phase studies have demonstrated the safety and tolerability of various maintenance approaches following HCT, the results of several ongoing randomized prospective studies will be required to determine the clinical efficacy needed to expand this approach from experimental to standard of care.

  View details for DOI 10.1080/10428194.2016.1205744

  View details for PubMedID 27685315

• Impact of Higher-Dose Total Body Irradiation Conditioning on Outcome of an Allogeneic Hematopoietic Cell Transplant (HCT) in the Modern Era Sabloff, M., Wang, T., Zhu, X., Artz, A. S., Adekola, K., Abraham, A., Auletta, J. J., Battiwalla, M., Beitinjaneh, A., Bredeson, C. N., Martino Bufarull, R., Cahn, J., Cerny, J., Chhabra, S., Copelan, E. A., Daly, A., Dias, A., Angel Diaz, M., Freytes, C. O., Gale, R., Ganguly, S., Hale, G. A., Hamilton, B., Hashmi, S. K., Hematti, P., Hildebrandt, G. C., Holmberg, L. A., Hong, S., Kekre, N., Lazarus, H. M., Lazaryan, A., Luger, S. M., Muffly, L., Nagler, A., Nishihori, T., Norkin, M., Olsson, R., Perales, M., Rashidi, A., Romee, R., Saad, A., Seo, S., Ulrickson, M. L., Ustun, C., Wirk, B. M., Woolfrey, A. E., Yared, J., Pasquini, M. C., Mineishi, S. ELSEVIER SCIENCE INC. 2017: S81-S82

  View details for Web of Science ID 000540635000081

• Integrating cancer survivorship care into allogeneic BMT recovery. Bugos, K., Stenger, S., Smith, A., Johnston, L., Gross, M., Knight, G., Lambert, S., Muffly, L. S. AMER SOC CLINICAL ONCOLOGY. 2017

  View details for Web of Science ID 000443300500037

• My Patient, the Superhero. Journal of clinical oncology Muffly, L. 2017: JCO2016696005-?

  View details for DOI 10.1200/JCO.2016.69.6005

  View details for PubMedID 28165900

• Pharmacologic maintenance strategies following allogeneic hematopoietic cell transplantation for acute myeloid leukemia. Leuk Lymphoma CJ, L., P, S., L, M. 2017; 58 (3): 516-527
• HLA-mismatched unrelated donor transplantation using TLI-ATG conditioning has a low risk of GVHD and potent antitumor activity. Blood advances Spinner, M. A., Fernández-Viña, M. n., Creary, L. E., Quinn, O. n., Elder, L. n., Arai, S. n., Johnston, L. J., Meyer, E. H., Miklos, D. B., Muffly, L. S., Negrin, R. S., Shizuru, J. A., Weng, W. K., Laport, G. G., Strober, S. n., Lowsky, R. n., Rezvani, A. R. 2017; 1 (17): 1347–57

  Abstract

  Many patients lack a fully HLA-matched donor for hematopoietic cell transplantation (HCT), and HLA mismatch is typically associated with inferior outcomes. Total lymphoid irradiation and antithymocyte globulin (TLI-ATG) is a nonmyeloablative conditioning regimen that is protective against graft-versus-host disease (GVHD), and we hypothesized that the protective effect would extend beyond HLA-matched donors. We report outcomes for all consecutively transplanted patients at Stanford University from December 2001 through May 2015 who received TLI-ATG conditioning and HCTs from 8 to 9 out of 10 HLA-mismatched unrelated donors (MMUDs, N = 72) compared with 10 out of 10 HLA-matched unrelated donors (MUDs, N = 193). The median age of the patients was 60 years with a median follow-up of 2 years, and there was a similar distribution of lymphoid and myeloid malignancies in both cohorts. There were no significant differences between MMUD and MUD cohorts in overall survival (46% vs 46% at 5 years, P = .86), disease-free survival (38% vs 28% at 5 years, P = .25), nonrelapse mortality (17% vs 12% at 2 years, P = .34), acute GVHD grades III-IV (6% vs 3% at day +100, P = .61), or chronic GVHD (39% vs 35% at 5 years, P = .49). There was a trend toward less relapse in the MMUD cohort (45% vs 60% at 5 years, hazard ratio: 0.71, P = .094), which was significant for patients with lymphoid malignancies (29% vs 57% at 5 years, hazard ratio: 0.55, P = .044). Achieving full donor chimerism was strongly associated with lower relapse rates. TLI-ATG conditioning may overcome the traditionally poorer outcome associated with HLA-mismatched donors and may be particularly well suited for patients with lymphoid malignancies who lack HLA-matched donors.

  View details for PubMedID 29296777

• Allogeneic Transplants from HLA-Mismatched Unrelated Donors Using Total Lymphoid Irradiation and Antithymocyte Globulin Conditioning Retain a Low Risk of Graft-Versus-Host Disease and Non-Relapse Mortality with at Least As Potent Anti-Tumor Activity As with Matched Unrelated Donors Spinner, M. A., Vina, M., Elder, L., Arai, S., Johnston, L., Meyer, E., Miklos, D., Muffly, L., Negrin, R. S., Shizuru, J., Weng, W., Laport, G. G., Strober, S., Lowsky, R., Rezvani, A. R. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394452507149

• Rate of Rise of EBV Viral Load By Quantitative PCR after Allogeneic Transplantation Correlates with PTLD Facilitates Timely Institution of Rituximab Muffly, L. S., Shiraz, P., Nguyen, I. T., Brown, J. M. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394452506195

• Adolescent and Young Adult Oncology Patients with Acute Lymphoblastic Leukemia: Shifting Location of Care over Time Alvarez, E., Muffly, L. S., Li, Q., Brunson, A. M., Wun, T., Chamberlain, L., Keegan, T. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394452700052

• Phase I Study of CD8 Memory T-Cell Donor Lymphocyte Infusion for Relapse of Hematologic Malignancies Following Matched Related Donor Allogeneic Hematopoietic Cell Transplantation Muffly, L. S., Sheehan, K., Armstrong, R., Tate, K., Tudisco, C., Rezvani, A. R., Miklos, D., Arai, S., Shizuru, J., Johnston, L., Meyer, E., Weng, W., Laport, G. G., Negrin, R. S., Strober, S., Lowsky, R. AMER SOC HEMATOLOGY. 2016

  View details for Web of Science ID 000394452506182

• Symptom burdens and coping strategies in adolescent and young adult (AYA) cancer survivors with hematologic malignancies. Hlubocky, F. J., Muffly, L. S., Gomez, J. X., Breitenbach, K., McNeer, J., Stock, W., Daugherty, C. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/jco.2016.34.26_suppl.256

  View details for Web of Science ID 000443269000247

• Adoption of pediatric-inspired acute lymphoblastic leukemia regimens by adult oncologists treating adolescents and young adults: A population-based study. Cancer Muffly, L., Lichtensztajn, D., Shiraz, P., Abrahão, R., McNeer, J., Stock, W., Keegan, T., Gomez, S. L. 2016

  Abstract

  Studies have demonstrated superior outcomes for adolescent and young adult (AYA) patients with acute lymphoblastic leukemia (ALL) who are treated using pediatric versus adult therapeutic regimens. To the best of our knowledge, whether adult oncologists in the United States have adopted this approach to ALL in AYA patients is currently unknown. The objective of the current study was to provide a population-based description of ALL treatment patterns in AYA individuals over the past decade.Data regarding AYA patients aged 15 to 39 years and diagnosed with ALL between 2004 and 2014 while living in the Greater Bay Area were obtained from the Greater Bay Area Cancer Registry (GBACR). Treating facilities were designated as pediatric or adult centers; induction treatment regimens were abstracted from registry text data fields.Of 304 patients diagnosed in the GBACR catchment region, complete treatment data were available for 229 (75%). The location of care was identified for 296 patients (97%) treated at 31 unique centers. Approximately 70% of AYA patients received induction therapy at an adult treatment center. All AYA patients who were treated at pediatric centers received pediatric ALL regimens. Among AYA patients treated by adult oncologists with complete treatment data, none received a pediatric regimen before 2008. Between 2008 and 2012, while the US Adult Intergroup C10403 pediatric-inspired ALL protocol was open to accrual, 31% of AYA patients treated by adult oncologists received pediatric regimens. This rate fell to 21% from 2013 through 2014. Adult facilities treating ≥ 2 AYA patients with ALL per year captured in the GBACR were more likely to administer pediatric regimens than lower volume centers (P = .03).As of 2014, only a minority of AYA patients with ALL received pediatric ALL regimens at adult cancer centers. Cancer 2017;122-130. © 2016 American Cancer Society.

  View details for DOI 10.1002/cncr.30322

  View details for PubMedID 27622953

  View details for PubMedCentralID PMC5161602

• Validation of the hematopoietic cell transplantation-specific comorbidity index in non-myeloablative allogeneic stem cell transplantation. Veeraputhiran, M., Arai, S., Lowsky, R., Miklos, D., Meyer, E., Muffly, L. S., Negrin, R., Rezvani, A. R., Shizuru, J., Weng, W., Johnston, L. J. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.7046

  View details for Web of Science ID 000404711504181

• Death anxiety, psychological distress, and quality of life (QOL) in adolescent and young adult (AYA) cancer patients with hematologic malignancies in early survivorship. Hlubocky, F. J., Muffly, L. S., Gomez, J. X., Breitenbach, K., Cella, D., McNeer, J., Stock, W., Daugherty, C. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.10073

  View details for Web of Science ID 000404712500061

• Financial toxicity in children, adolescent, and young adult cancer patients and their families: A large national registry analysis from the family reach foundation Muffly, L. S., Tardif, C., de Souza, J. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_suppl.6615

  View details for Web of Science ID 000404711503137

• Long-term outcomes of high-dose melphalan and carmustine followed by autologous hematopoietic cell transplantation for multiple myeloma. Neppalli, A., Shizuru, J., Johnston, L. J., Muffly, L. S., Weng, W., Negrin, R., Meyer, E., Laport, G., Lowsky, R., Arai, S., Miklos, D., Rezvani, A. R. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/JCO.2016.34.15_supp1.8026

  View details for Web of Science ID 000404711505181

• Psychological morbidities in adolescent and young adult blood cancer patients during curative-intent therapy and early survivorship. Cancer Muffly, L. S., Hlubocky, F. J., Khan, N., Wroblewski, K., Breitenbach, K., Gomez, J., McNeer, J. L., Stock, W., Daugherty, C. K. 2016; 122 (6): 954-961

  Abstract

  Adolescents and young adults (AYAs) with cancer face unique psychosocial challenges. This pilot study was aimed at describing the prevalence of psychological morbidities among AYAs with hematologic malignancies during curative-intent therapy and early survivorship and at examining provider perceptions of psychological morbidities in their AYA patients.Patients aged 15 to 39 years with acute leukemia, non-Hodgkin lymphoma, or Hodgkin lymphoma who were undergoing curative-intent therapy (on-treatment group) or were in remission within 2 years of therapy completion (early survivors) underwent a semistructured interview that incorporated measures of anxiety, depression, and posttraumatic stress (PTS). A subset of providers (n = 15) concomitantly completed a survey for each of the first 30 patients enrolled that evaluated their perception of each subject's anxiety, depression, and PTS.Sixty-one of 77 eligible AYAs participated. The median age at diagnosis was 26 years (range, 15-39 years), 64% were male, and 59% were non-Hispanic white. On-treatment demographics differed significantly from early-survivor demographics only in the median time from diagnosis to interview. Among the 61 evaluable AYAs, 23% met the criteria for anxiety, 28% met the criteria for depression, and 13% met the criteria for PTS; 46% demonstrated PTS symptomatology. Thirty-nine percent were impaired in 1 or more psychological domains. Psychological impairments were as frequent among early survivors as AYAs on treatment. Provider perceptions did not significantly correlate with patient survey results.AYAs with hematologic malignancies experience substantial psychological morbidities while they are undergoing therapy and during early survivorship, with more than one-third of the patients included in this study meeting the criteria for anxiety, depression, or traumatic stress. This psychological burden may not be accurately identified by their oncology providers. Cancer 2015. © 2015 American Cancer Society.

  View details for DOI 10.1002/cncr.29868

  View details for PubMedID 26749023

• Increasing Use of Allogeneic Hematopoietic Cell Transplantation (HCT) in Patients Age 70 Years and Older: A CIBMTR Study of Trends and Outcomes Muffly, L., Pasquini, M. C., Martens, M., Brazauskas, R., Zhu, X., Adekola, K., Aljurf, M. D., Artz, A. S., Bajel, A., Ballen, K. K., Battiwalla, M., Beitinjaneh, A., Cahn, J., Carabasi, M., Chen, Y., Chhabra, S., Ciurea, S. O., Copelan, E. A., D'Souza, A., Edwards, J., Freytes, C. O., Fung, H. C., Gale, R., Giralt, S. A., Hashmi, S. K., Hematti, P., Hildebrandt, G. C., Ho, V. T., Jakubowski, A. A., Lazarus, H. M., McCarthy, P. L., Olin, R. L., Olsson, R., Rezvani, A., Rizzieri, D. A., Seftel, M., Seo, S., Sorror, M. L., Szer, J., Wood, W. A. ELSEVIER SCIENCE INC. 2016: S68–S69

  View details for DOI 10.1016/j.bbmt.2015.11.360

  View details for Web of Science ID 000370910300072

• Long-Term Outcomes of AML Patients Using Total Lymphoid Irradiation with Anti-Thymocyte Globulin Nakasone, H., Miklos, D. B., Meyer, E., Rezvani, A., Muffly, L., Weng, W., Arai, S., Johnston, L., Laport, G. G., Shizuru, J. A., Negrin, R., Strober, S., Lowsky, R. ELSEVIER SCIENCE INC. 2016: S204–S205

  View details for DOI 10.1016/j.bbmt.2015.11.598

  View details for Web of Science ID 000370910300287

• Substance use, psychological distress, and quality of life (QOL) in adolescent and young adult (AYA) cancer patients with hematologic malignancies in early survivorship. Hlubocky, F. J., Muffly, L. S., Gomez, J., Breitenbach, K., Lappe, M., Stock, W., Daugherty, C. AMER SOC CLINICAL ONCOLOGY. 2016

  View details for DOI 10.1200/jco.2016.34.3_suppl.219

  View details for Web of Science ID 000378109500209

• Donor-Derived CIK Cell Infusion As Consolidative Therapy after Non-Myeloablative Allogeneic Transplant in Patients with Myeloid Neoplasms Narayan, R., Benjamin, J., Laport, G., Tian, L., Tate, K., Elder, L., Galvez, L., Armstrong, R., Sheehan, K., Lowsky, R., Arai, S., Johnston, L., Miklos, D., Muffly, L. S., Rezvani, A. R., Shizuru, J., Weng, W., Strober, S., Negrin, R., Meyer, E. AMER SOC HEMATOLOGY. 2015

  View details for Web of Science ID 000368020104114

• The overlooked COST of multiple myeloma. The Lancet. Haematology de Souza, J. A., Muffly, L. 2015; 2 (10): e394-5

  View details for DOI 10.1016/S2352-3026(15)00192-1

  View details for PubMedID 26686034

• Secondary solid cancer screening following hematopoietic cell transplantation. Bone marrow transplantation INAMOTO, Y., Shah, N. N., Savani, B. N., Shaw, B. E., Abraham, A. A., Ahmed, I. A., Akpek, G., Atsuta, Y., Baker, K. S., Basak, G. W., Bitan, M., DeFilipp, Z., GREGORY, T. K., Greinix, H. T., Hamadani, M., Hamilton, B. K., Hayashi, R. J., Jacobsohn, D. A., Kamble, R. T., Kasow, K. A., Khera, N., Lazarus, H. M., Malone, A. K., Lupo-Stanghellini, M. T., Margossian, S. P., Muffly, L. S., Norkin, M., Ramanathan, M., Salooja, N., Schoemans, H., Wingard, J. R., Wirk, B., Wood, W. A., Yong, A., Duncan, C. N., Flowers, M. E., Majhail, N. S. 2015; 50 (8): 1013-1023

  Abstract

  Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

  View details for DOI 10.1038/bmt.2015.63

  View details for PubMedID 25822223

  View details for PubMedCentralID PMC4989866

• Patient Selection for Allogeneic Hematopoietic Cell Transplantation (HCT): the Evolution of HCT Risk Assessment. Current hematologic malignancy reports Muffly, L. 2015; 10 (1): 28-34

  Abstract

  The use of allogeneic hematopoietic cell transplantation is expanding, with disproportionate growth witnessed in older adults with hematologic malignancies. As the chronological age barrier to transplant fades, refining the pre-hematopoietic cell transplantation (HCT) risk assessment to better capture host health status and disease characteristics is essential. This review summarizes recent efforts to move the field forward towards achieving this goal. Many of these risk assessment tools are currently included in prospective clinical trials; routine clinical use requires greater understanding of how to best incorporate this new information into HCT decision making.

  View details for DOI 10.1007/s11899-014-0241-2

  View details for PubMedID 25500987

• Peripheral T-cell lymphomas in a large US multicenter cohort: prognostication in the modern era including impact of frontline therapy ANNALS OF ONCOLOGY Abramson, J. S., Feldman, T., Kroll-Desrosiers, A. R., Muffly, L. S., Winer, E., Flowers, C. R., Lansigan, F., Nabhan, C., Nastoupil, L. J., Nath, R., Goy, A., Castillo, J. J., Jagadeesh, D., Woda, B., Rosen, S. T., Smith, S. M., Evens, A. M. 2014; 25 (11): 2211-2217

  Abstract

  Optimal frontline therapy for peripheral T-cell lymphoma (PTCL) in the modern era remains unclear.We examined patient characteristics, treatment, and outcomes among 341 newly diagnosed PTCL patients from 2000 to 2011. Outcome was compared with a matched cohort of diffuse large B-cell lymphoma (DLBCL) patients, and prognostic factors were assessed using univariate and multivariate analyses.PTCL subtypes included PTCL, not otherwise specified (PTCL-NOS) (31%), anaplastic large T-cell lymphoma (ALCL) (26%), angioimmunoblastic T-cell lymphoma (23%), NK/T-cell lymphoma (7%), acute T-cell leukemia/lymphoma (6%), and other (7%). Median age was 62 years (range 18-95 years), and 74% had stage III-IV disease. Twenty-three (7%) patients received only palliative care whereas 318 received chemotherapy: CHOP-like regimens (70%), hyperCVAD/MA (6%), or other (18%). Thirty-three patients (10%) underwent stem-cell transplantation (SCT) in first remission. The overall response rate was 73% (61% complete); 24% had primary refractory disease. With 39-month median follow-up, 3-year progression-free survival (PFS) and overall survival (OS) were 32% and 52%. PFS and OS for PTCL patients were significantly inferior to matched patients with DLBCL. On multivariate analysis, stage I-II disease was the only significant pretreatment prognostic factor [PFS: hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.34-0.85, P = 0.007; OS: HR 0.42, 95% CI 0.22-0.78, P = 0.006]. ALK positivity in ALCL was prognostic on univariate analysis, but lost significance on multivariate analysis. The most dominant prognostic factor was response to initial therapy (complete response versus other), including adjustment for stage and SCT [PFS: HR 0.19, 95% CI 0.14-0.28, P < 0.0001; OS: HR 0.26, 95% CI 0.17-0.40, P < 0.0001]. No overall survival difference was observed based on choice of upfront regimen or SCT in first remission.This analysis identifies early-stage disease and initial treatment response as dominant prognostic factors in PTCL. No clear benefit was observed for patients undergoing consolidative SCT. Novel therapeutic approaches for PTCL are critically needed.

  View details for DOI 10.1093/annonc/mdu443

  View details for Web of Science ID 000344644200016

  View details for PubMedID 25193992

  View details for PubMedCentralID PMC4481543

• Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients HAEMATOLOGICA Muffly, L. S., Kocherginsky, M., Stock, W., Chu, Q., Bishop, M. R., Godley, L. A., Kline, J., Liu, H., Odenike, O. M., Larson, R. A., Van Besien, K., Artz, A. S. 2014; 99 (8): 1373-1379

  Abstract

  Allogeneic hematopoietic cell transplantation is increasingly utilized in older adults. This study prospectively evaluated the prognostic utility of geriatric assessment domains prior to allogeneic transplantation in recipients aged 50 years and over. Geriatric assessment was performed prior to transplant, and included validated measures across domains of function and disability, comorbidity, frailty, mental health, nutritional status, and systemic inflammation. A total of 203 patients completed geriatric assessment and underwent transplant. Median age was 58 years (range 50-73). After adjusting for established prognostic factors, limitations in instrumental activities of daily living (HR 2.38, 95%CI: 1.59-3.56; P<0.001), slow walk speed (HR 1.80, 95%CI: 1.14-2.83; P=0.01), high comorbidity by hematopoietic cell transplantation-specific comorbidity index (HR 1.56, 95%CI: 1.07-2.28; P=0.02), low mental health by short-form-36 mental component summary (HR 1.67, 95%CI: 1.13-2.48; P=0.01), and elevated serum C-reactive protein (HR 2.51, 95%CI: 1.54-4.09; P<0.001) were significantly associated with inferior overall survival. These associations were more pronounced in the cohort 60 years and over. Geriatric assessment measures confer independent prognostic utility in older allogeneic transplant recipients. Implementation of geriatric assessment prior to allogeneic transplantation may aid appropriate selection of older adults.

  View details for DOI 10.3324/haematol.2014.103655

  View details for Web of Science ID 000342834300022

  View details for PubMedID 24816237

  View details for PubMedCentralID PMC4116837

• Hematopoietic cell transplantation in T-cell non-Hodgkin's lymphomas CANCER CONSULT: EXPERTISE FOR CLINICAL PRACTICE Muffly, L. S., Smith, S. M., Abutalib, S. A., Markman, M. 2014: 339-344

  View details for Web of Science ID 000351672800054

• Prognosis in diffuse large B-cell lymphoma The Picture Continues to Come Into Focus CANCER Muffly, L. S., Smith, S. M. 2013; 119 (6): 1129-1131

  View details for DOI 10.1002/cncr.27860

  View details for Web of Science ID 000315696600005

  View details for PubMedID 23212789

• Pilot Study of Comprehensive Geriatric Assessment (CGA) in Allogeneic Transplant: CGA Captures a High Prevalence of Vulnerabilities in Older Transplant Recipients BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION Muffly, L. S., Boulukos, M., Swanson, K., Kocherginsky, M., del Cerro, P., Schroeder, L., Pape, L., Extermann, M., Van Besien, K., Artz, A. S. 2013; 19 (3): 429-434

  Abstract

  Comprehensive geriatric assessment (CGA) is frequently used in oncology to measure the health status of older adults with cancer, but it has not been studied in allogeneic hematopoietic cell transplantation (HCT). We conducted a prospective pilot study of CGA in allogeneic HCT recipients aged ≥50 years to examine the prevalence of vulnerabilities in this population. Patients aged ≥50 years eligible for HCT were enrolled. CGA consisted mainly of self-reported, performance-based, and chart-extracted measures evaluating domains of comorbidity, physical and mental function, frailty, disability, and nutrition. Of 238 eligible patients, 166 completed CGA and underwent HCT. Only 1% had a Zubrod Performance Status score >1; 44% had high comorbidity defined by the Hematopoietic Cell Transplantation Comorbidity Index, and 66% had high comorbidity defined by the Cumulative Illness Rating Scale-Geriatrics. The presence of additional vulnerability was frequent. Disability was present in 40% by Instrumental Activities of Daily Living. Self-reported physical and mental function were significantly lower than population age group norms, 58% were pre-frail, and 25% were frail. Among those with Zubrod Performance Status score of 0, 28% demonstrated disability, 58% were pre-frail, 15% were frail, 35% reported low physical function, and 55% reported low mental function. CGA uncovers a substantial prevalence of undocumented impairments in functional status, frailty, disability, and mental health in older allogeneic HCT recipients.

  View details for DOI 10.1016/j.bbmt.2012.11.006

  View details for Web of Science ID 000315425700015

  View details for PubMedID 23160006

• Microwave imaging for neoadjuvant chemotherapy monitoring: initial clinical experience BREAST CANCER RESEARCH Meaney, P. M., Kaufman, P. A., Muffly, L. S., Click, M., Poplack, S. P., Wells, W. A., Schwartz, G. N., di Florio-Alexander, R. M., Tosteson, T. D., Li, Z., Geimer, S. D., Fanning, M. W., Zhou, T., Epstein, N. R., Paulsen, K. D. 2013; 15 (2)

  Abstract

  Microwave tomography recovers images of tissue dielectric properties, which appear to be specific for breast cancer, with low-cost technology that does not present an exposure risk, suggesting the modality may be a good candidate for monitoring neoadjuvant chemotherapy.Eight patients undergoing neoadjuvant chemotherapy for locally advanced breast cancer were imaged longitudinally five to eight times during the course of treatment. At the start of therapy, regions of interest (ROIs) were identified from contrast-enhanced magnetic resonance imaging studies. During subsequent microwave examinations, subjects were positioned with their breasts pendant in a coupling fluid and surrounded by an immersed antenna array. Microwave property values were extracted from the ROIs through an automated procedure and statistical analyses were performed to assess short term (30 days) and longer term (four to six months) dielectric property changes.Two patient cases (one complete and one partial response) are presented in detail and demonstrate changes in microwave properties commensurate with the degree of treatment response observed pathologically. Normalized mean conductivity in ROIs from patients with complete pathological responses was significantly different from that of partial responders (P value = 0.004). In addition, the normalized conductivity measure also correlated well with complete pathological response at 30 days (P value = 0.002).These preliminary findings suggest that both early and late conductivity property changes correlate well with overall treatment response to neoadjuvant therapy in locally advanced breast cancer. This result is consistent with earlier clinical outcomes that lesion conductivity is specific to differentiating breast cancer from benign lesions and normal tissue.

  View details for DOI 10.1186/bcr3418

  View details for Web of Science ID 000330612000018

  View details for PubMedID 23621959

  View details for PubMedCentralID PMC3672734

• Characteristics and outcomes of extranodal NK/t-cell lymphoma (ENKL): A North American (NA) multi-institutional experience. 48th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) Maeda, L. S., Geiger, J. L., Savage, K. J., Rose, J., Pinter-Brown, L. C., Lunning, M. A., Abramson, J. S., Bartlett, N., Vose, J., Drape, J., Muffly, L. S., McMillan, A., Evens, A. M., Smith, S. M., Horwitz, S. M., Ansell, S. M., Advani, R. AMER SOC CLINICAL ONCOLOGY. 2012

  View details for Web of Science ID 000318009803765

• Evaluation of Breast Tumor Response to Neoadjuvant Chemotherapy with Tomographic Diffuse Optical Spectroscopy: Case Studies of Tumor Region-of-Interest Changes RADIOLOGY Jiang, S., Pogue, B. W., Carpenter, C. M., Poplack, S. P., Wells, W. A., Kogel, C. A., Forero, J. A., Muffly, L. S., Schwartz, G. N., Paulsen, K. D., Kaufman, P. A. 2009; 252 (2): 551-560

  Abstract

  To evaluate two methods of summarizing tomographic diffuse optical spectroscopic (DOS) data through region-of-interest (ROI) analysis to differentiate complete from incomplete responses in patients with locally advanced breast cancer undergoing neoadjuvant treatment and to estimate the standard deviations of these methods for power analysis of larger study designs in the future.Subjects participating in the HIPAA-compliant imaging study, approved by the institutional review board, provided written informed consent and were compensated for their examination participation. Seven of 16 cases in women with complete study data were analyzed by using both fixed- and variable-size (full-width-at-half-maximum) ROI measures of the DOS total hemoglobin concentration (Hb(T)), blood oxygen saturation, water fraction, optical scattering amplitude, and scattering power in the ipsilateral and contralateral breasts. Postsurgical histopathologic analysis was used to categorize patients as having a complete or incomplete treatment response.Average normalized change in Hb(T) was the only DOS parameter to show significant differences (P < or = .05) in the pathologic complete response (pCR) and pathologic incomplete response (pIR) outcomes in seven patients. Mean values of the changes for fixed-size ROIs were -64.2% +/- 50.8 (standard deviation) and 16.9% +/- 38.2 for the pCR and pIR groups, respectively, and those for variable-size ROIs were -96.7% +/- 91.8, and 14.1% +/- 26.7 for the pCR and pIR groups, respectively.Tomographic DOS may provide findings predictive of therapeutic response, which could lead to superior individualized patient treatment.http://radiology.rsnajnls.org/cgi/content/full/2522081202/DC1.

  View details for DOI 10.1148/radiol.2522081202

  View details for Web of Science ID 000268875900031

  View details for PubMedID 19508985

  View details for PubMedCentralID PMC2753781