Lianna Marks

All Publications

• Dose-dense chemotherapy enables elimination of RT for majority of low-risk pediatric Hodgkin lymphoma: PHC study HOD08. Blood Flerlage, J. E., Feraco, A. M., Zhou, Y., Zheng, Y., Liang, J., Lucas, J. T., Friedmann, A. M., Weinstein, H. J., Yock, T. I., Shulkin, B. L., Kaste, S. C., Marks, L. J., Ehrhardt, M. J., Dixon, S. B., Howard, S., de Alarcon, P., Luna-Fineman, S., Geddis, A. E., Larsen, E. C., Marcus, K. J., Billett, A., Donaldson, S. S., Hudson, M. M., Metzger, M. L., Krasin, M. J., Link, M. P. 2026

  Abstract

  The Pediatric Hodgkin Consortium (PHC) hypothesized that increasing chemotherapeutic dose-density for Hodgkin lymphoma (HL) they could increase the complete response rate among favorable risk patients with HL after 8 weeks of Stanford V compared to 8 weeks of VAMP. This would translate to a decrease in patients who required radiation therapy (RT) to achieve a cure. HOD08 (NCT00846742) was a phase II multicenter investigator-initiated single- arm trial for patients ≤ 21 years of age with previously untreated stage IA or IIA HL without mediastinal bulk or extranodal disease extension and fewer than three sites of disease. Treatment consisted of a modified 8-week Stanford V regimen (vinblastine, doxorubicin, vincristine, bleomycin, mechlorethamine, etoposide and prednisone). Modified tailored field RT was administered only to disease sites achieving less than a CR. The primary objective was to increase CR rate after 8 weeks of chemotherapy by at least 20% (from an estimated 44% to 64%) compared to patients treated on a previous trial (HOD99). HOD08 enrolled 85 patients with HL and 72 were evaluable for the primary objective of whom 55 (76.4%) achieved a CR at all sites and did not receive RT. The 5-year event-free survival (EFS) and overall survival (OS) rates for the entire cohort were 87.4% (95% confidence interval (CI) 80.4%-95.0%) and 98.7% (95% CI 96.2%-100%), respectively. A dose-dense modified Stanford V regimen reduced the proportion of low-risk pediatric patients with HL who received RT while maintaining excellent outcomes. NCT00846742.

  View details for DOI 10.1182/blood.2025029535

  View details for PubMedID 41529162

• Abnormal immunoglobulin expression and B-cell follicle organization in inborn errors of immunity/primary immunodeficiency. Virchows Archiv : an international journal of pathology Naor, S., Schiby, G., Adam, E., Somech, R., Molchanov, Y., Barshack, I., Lewis, D. B., Marks, L., Gratzinger, D. 2025

  Abstract

  Patients with inborn errors of immunity/primary immunodeficiency (IEI/PID) frequently present with reactive lymphadenopathy which is biopsied to rule out lymphoma or infection. We asked whether reactive lymphoid tissue from an international cohort of 35 patients with IEI/PID contains diagnostic clues to the underlying immune dysfunction as compared to 13 control pediatric patients. To this end, we investigated abnormalities of B-cell follicle architecture and Immunoglobulin G (IgG) + class-switched (CS) versus IgM/IgD + non-IgG-CS Ig production. Abnormalities of B-cell follicles including absent or naked germinal centers (GCs) and/or increased T follicular helper(TFH) cells within GCs were seen in 45.7% (16/35) of IEI/PIDs and 15.4% (2/13) of controls (X2 = 3.7520, p = 0.054). There was a statistically significant association of B-cell follicle abnormalities with infectious (X2 = 5.148, p = 0.023) but not autoimmune history. Abnormal IgM + , IgD + , IgG + and/or CD138 + plasmablast/plasma cell (PB/PC) density was observed in 79.4% of IEI/PIDs (27/34) as compared to 7.7% of controls (1/13, X2 = 20.085, p < 0.001). Isolated deficiency of IgG CS PB/PC was present in 42% (12/33) of IEI/PID biopsies and in no control patients, 0% (0/13, X2 = 6.396, p = 0.011). There was a strong and highly statistically significant positive correlation between IgG + PB/PC density and serum IgG (Kendall's tau-b 0.567, asymptotic standard error 0.129, approximate significance < 0.001). There was also a statistically significant association of PB/PC abnormalities with infectious (X2 = 12.024, p < 0.001) but not autoimmune history. Assessment of B-cell follicle architecture and Ig production may play a role in identifying patients with unexplained reactive lymphadenopathy who would benefit from immunologic evaluation.

  View details for DOI 10.1007/s00428-025-04378-x

  View details for PubMedID 41460331

  View details for PubMedCentralID 5292996

• Langerhans Cell Histiocytosis in Cardiofaciocutaneous Syndrome. American journal of medical genetics. Part A Keehan, L., Sleightholm, R., Marks, L. J., Stevenson, D. A., Niehaus, A. D. 2025: e64294

  Abstract

  The Ras/mitogen-activated protein kinase (RAS/MAPK) pathway regulates cell proliferation, and dysregulation of this pathway has been linked to the increased risk of malignancy in a subset of disorders known as RASopathies (e.g., NF1, Costello syndrome, Noonan syndrome). However, reports of malignancy are rare in cardiofaciocutaneous (CFC) syndrome, which is caused by heterozygous pathogenic variants in BRAF, MAP2K1, MAP2K2, and KRAS. Somatic pathogenic variants in BRAF are one of the most common drivers of Langerhans cell histiocytosis (LCH), a neoplastic disorder that can present with lesions in a variety of locations. However, despite the association of somatic BRAF variants and LCH, individuals with CFC syndrome are not thought to have higher rates of LCH. Here, we report two individuals with CFC syndrome and LCH and review the literature examining this potential association.

  View details for DOI 10.1002/ajmg.a.64294

  View details for PubMedID 41174928

• Distinct cell state ecosystems for nodular lymphocyte-predominant Hodgkin lymphoma. Nature communications Subramanian, A., Su, S., Flerlage, J., Alig, S., Younes, S., Marks, L. J., Pinnix, C., Vega, F., Steiner, R., Kumar, P., Mocikova, H., Sykorova, A., Prochazka, V., Milito, C., Allen, P., Paulino, D., Ramsay, A., Flerlage, T., Palese, M., West, R., Zhu, C., Noordenbos, T., Schroers-Martin, J., Zhao, S., Park, N. J., Kalbasi, A., Moding, E. J., Newman, A. M., Advani, R. H., Hoppe, R. T., Diehn, M., Natkunam, Y., Alizadeh, A. A., Binkley, M. S. 2025; 16 (1): 8473

  Abstract

  Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare cancer, and few studies have comprehensively investigated the immune microenvironment and rare lymphocyte-predominant (LP) cells. Here we develop a NLPHL specific lymphocyte-predominant ecotype (LPE) model to identify 34 distinct cell states across 14 cell types that co-occur within 3 LPEs for 171 cases. LPE1 and LPE2 were characterized by immunosuppressive microenvironments with high expression of B2M on LP cells, CD8 T-cell exhaustion, immune checkpoint genes expressed by follicular T-cells, and an improved freedom from progression compared to LPE3 in training (n = 109, with 65% LPE1/2) and validation cohorts (n = 62, with 61% LPE1/2). We validate the co-occurrence and co-localization of cell states using spatial transcriptomics. Protein expression of HLA-I and HLA-II on LP cells and SSTR2 on dendritic cells was predictive of LPE1 (C-statistic=0.69), LPE2 (C-statistic=0.79), and LPE3 (C-statistic=0.60). This study establishes a clinically relevant biologic categorization for NLPHL.

  View details for DOI 10.1038/s41467-025-63339-9

  View details for PubMedID 41006203

  View details for PubMedCentralID PMC12475200

• IMPACT OF EPSTEIN BARR VIRUS (EBV) STATUS OF LESIONS, 2016 WHO HISTOLOGIC GRADE AND TIME OF ONSET ON OUTCOME OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD) IN PEDIATRIC SOLID ORGAN TRANSPLANT (SOT) AND HEMATOPOIETIC STEM CELL TRANSPLANT (HCT) RECIPIENTS: RESULTS OF A PROSPECTIVE/RETROSPECTIVE MULTICENTER STUDY Green, M., Marks, L. J., Agarwal, M., Goss, C. W., Dharnidharka, V. R. WILEY. 2025

  View details for Web of Science ID 001606152800081

• METABOLIC-ONLY RESPONSE ASSESSMENT ALLOWS FOR OMISSION OF RESIDUAL NODE RADIATION THERAPY (RNRT) FOR THE MAJORITY OF PATIENTS WITH CLASSICAL HODGKIN LYMPHOMA (cHL) WHILE MAINTAINING EXCELLENT EVENT FREE (EFS) AND OVERALL SURVIVAL (OS): A REPORT FROM THE PEDIATRIC HODGKIN CONSORTIUM'S PHASE 2 STUDY cHOD17 (NCT03755804) Flerlage, J. E., Feraco, A. M., Zhou, Y., Zheng, Y., Lucas, J. T., Dixon, S. B., Blake, J., Wilemon, L., Roberts, B. A., Marks, L. J., Friedmann, A. M., MacDonald, S., Weinstein, H. J., de Alarcon, P., Larsen, E. C., Yock, T. I., Hiniker, S., Bolen, C., Voss, S. D., Link, M. P., Ehrhardt, M. J., Pediatric Hodgkin Consortium PERGAMON-ELSEVIER SCIENCE LTD. 2025

  View details for Web of Science ID 001603165200100

• IMPACT OF TIME OF ONSET OF PEDIATRIC POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER OUTCOMES: RESULTS FROM A PROSPECTIVE/RETROSPECTIVE MULTICENTER STUDY Marks, L. J., Green, M., Agarwal, M., Goss, C. W., Dharnidharka, V. R., PTLD-MSMS Grp PERGAMON-ELSEVIER SCIENCE LTD. 2025

  View details for DOI 10.1016/j.leukres.2025.107964

  View details for Web of Science ID 001603165200032

• Primary Splenic Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL): First Reported Case in a Young Child. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society Vergara, J. S., Marks, L. J., Silva, O. 2025: 10935266251368431

  Abstract

  Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare subtype of B-cell lymphoma. NLPHL is usually indolent, involves lymph nodes and shows a favorable prognosis with high overall survival. In a minority of cases, patients may present and/or progress to advanced disease with involvement of the spleen, liver, and/or bone marrow. While splenic involvement by NLPHL is usually presumed evidence of advanced disease with poor prognosis, here we report to our knowledge, the first case of primary splenic NLPHL occurring in a child who showed no overt nodal disease and is currently free of disease 3 years post-splenectomy without additional treatment.

  View details for DOI 10.1177/10935266251368431

  View details for PubMedID 40873161

• Advances and updates in pediatric anaplastic large cell lymphoma. Blood advances Marks, L. J., Lowe, E. J., Kamdar, K. Y. 2025

  Abstract

  Anaplastic large cell lymphoma (ALCL) is a rare form of mature T-cell non-Hodgkin lymphoma. In pediatric patients, the majority of cases are Anaplastic Lymphoma Kinase (ALK)-positive. Despite intensive multi-agent chemotherapy regimens, treatment failure rates remain at 25-30%. Recent advancements in targeted therapies, notably ALK inhibitors and the anti-CD30 antibody-drug conjugate brentuximab vedotin, have demonstrated substantial activity in relapsed and refractory settings. Molecular detection of minimal disseminated disease (MDD) and minimal residual disease (MRD) offer improved prognostic stratification. For patients with relapsed or refractory disease, targeted therapies have increased treatment options, but more work needs to be done to define optimal treatment regimens, duration, and need for hematopoietic stem cell transplantation in this group. Immune therapies such as checkpoint inhibitors or Chimeric Antigen Receptor T-cell therapy provide additional therapeutic options. Incorporating targeted therapies and MDD/MRD assessments into clinical trials could significantly improve outcomes for pediatric and adolescent patients with ALCL.

  View details for DOI 10.1182/bloodadvances.2025015935

  View details for PubMedID 40690755

• Metabolic-only response assessment for omission of residual node radiation therapy (RNRT) for patients with classical Hodgkin lymphoma (cHL) and impact on event free (EFS) and overall survival (OS): A report from the Pediatric Hodgkin Consortium's phase 2 study cHOD17 (NCT03755804). Flerlage, J., Feraco, A., Zhou, Y., Zheng, Y., Lucas Jr, J., Rogers-Blake, J., Wilemon, L., Roberts, B. A., Marks, L., Friedmann, A., MacDonald, S. M., Weinstein, H. J., De Alarcon, P., Larsen, E., Yock, T. I., Hiniker, S. M., Bolen, C., Voss, S. D., Link, M., Ehrhardt, M. J., Pediat Hodgkin Consoritum LIPPINCOTT WILLIAMS & WILKINS. 2025: 10018

  View details for DOI 10.1200/JCO.2025.43.16_suppl.10018

  View details for Web of Science ID 001690358300010

• PTLD - It's Best to Face This Growing Challenge at the Start. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons Blosser, C. D., Marks, L. J., Dharnidharka, V. R. 2025

  View details for DOI 10.1016/j.ajt.2025.03.006

  View details for PubMedID 40064296

• PET Response and Outcome in Low-Risk Nodular Lymphocyte-Predominant Hodgkin Lymphoma: Children's Oncology Group Study AHOD03P1. Pediatric blood & cancer Marks, L. J., Wu, Y., McCarten, K. M., Renfro, L. A., Pei, Q., Kelly, K. M., Schwartz, C. L., Castellino, S. M., Appel, B. E. 2025: e31606

  Abstract

  A better understanding of positron emission tomography (PET) response in nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is critical for incorporating PET into prospective trials. PET scans from Children's Oncology Group study AHOD03P1 for patients less than 22 years with low-risk nLPHL, treated with three cycles of doxorubicin, vincristine, prednisone, and cyclophosphamide chemotherapy, were retrospectively reviewed and assigned Deauville 5-point scale (5PS) scores. Five-year post-PET event-free survival was 90.1% (80% CI: 85.2%-93.4%) for PET-negative (5PS 1-3) and 66.7% (80% CI: 36.4%-85.0%) for PET-positive (5PS 4-5) patients. PET response after three cycles of low-dose chemotherapy is predictive of relapse risk for low-risk nLPHL.

  View details for DOI 10.1002/pbc.31606

  View details for PubMedID 39953678

• Pediatric relapsed/refractory ALK+ anaplastic large cell lymphoma treatment and outcomes in the targeted drug era. Blood advances Marks, L. J., Ritter, V., Agrusa, J., Kamdar, K. Y., Rivers, J., Gardner, R. A., Ehrhardt, M. J., Devine, K. J., Phillips, C. A., Reilly, A. F., August, K., Weinstein, J. L., Satwani, P., Forlenza, C. J., Smith, C. M., Greer, C., Afify, Z., Lin, C. H., Belsky, J. A., Ding, H., Hoogstra, D., Toner, K., Link, M. P., Schultz, L. M., Lowe, E. J., Aftandilian, C. 2025

  Abstract

  Treatment options for patients with relapsed or refractory (R/R) anaplastic large cell lymphoma (ALCL) have increased in the era of targeted therapies such as brentuximab vedotin (BV) and Anaplastic Lymphoma Kinase (ALK) inhibitors. However, there is no standard treatment and limited published data evaluating their use. The goal of this retrospective study is to describe current real-world treatment and outcomes of pediatric, adolescent, and young adult patients with R/R ALK-positive ALCL. We conducted a retrospective, multi-institutional study identifying 81 patients with R/R ALK-positive ALCL ≤ 21 years old at initial diagnosis treated between 2011-2022 across 18 institutions. Median time from diagnosis to relapse was 8.9 months (range 2.6-131.9). Initial reinduction regimens included ALK inhibitor monotherapy (n=37, 46%), BV monotherapy (n=19, 23%), chemotherapy without targeted therapy (n=12, 15%), chemotherapy with targeted therapy (n=9, 11%), or vinblastine monotherapy (n=4, 5%) with 83% of patients achieving a complete response to initial reinduction regimen. Fifty-eight patients received a hematopoietic stem cell transplant (HSCT), 11 autologous and 48 allogeneic, with one receiving both. Duration of treatment for patients receiving BV or the ALK-inhibitor crizotinib (CZ) varied widely (BV 1-11 years; CZ 2-10 years). Five-year event-free survival 63% (95% CI 53-75%) and five-year overall survival 91% (95% CI 84-98%). This is the largest collection of patients with R/R ALK+ ALCL treated in the era of targeted therapy. Patients achieved excellent responses to ALK-inhibitor or BV monotherapy, but questions remain about duration of therapy and role of HSCT.

  View details for DOI 10.1182/bloodadvances.2024014745

  View details for PubMedID 39841960

• The Post-transplant Lymphoproliferative Disorders-Metagenomic Shotgun Microbial Sequencing (PTLD-MSMS) Study Methods and Protocol. Transplantation direct Dharnidharka, V. R., Wylie, K. M., Wylie, T. N., Ruzinova, M. B., Goss, C. W., Storch, G. A., Mehta-Shah, N., Byers, D., Walther, L., Jaza, L., Gu, H., Agarwal, M., Green, M., Moore, E., Swerdlow, S. H., Silveira, F., Marks, L. J., Gratzinger, D., Bagg, A., Law, S. C., Gandhi, M. 2024; 10 (11): e1723

  Abstract

  Post-transplant lymphoproliferative disorders (PTLDs) remain a feared complication of transplantation, with significant morbidity and mortality. The oncogenic Epstein-Barr virus (EBV) is a key pathogenic driver in 50%-80% of cases. Numerous prognostic indices, comprising multiple clinical, epidemiological and tumor characteristics, including EBV tumor positivity, do not consistently associate with worse patient survival, suggesting a potential role for EBV genome variants in determining outcome. However, the precision medicine tools for determining if a viral genome variant is pathogenic are very limited compared with human genome variants. Further, targeted studies have not implicated a specific viral etiological agent in EBV-negative PTLD. Using novel cutting-edge technologies, we are extracting viral nucleic acids from formalin-fixed, paraffin-embedded archived, or frozen PTLD tissues or plasma, to test for all vertebrate viruses simultaneously in an unbiased fashion, using metagenomic shotgun sequencing (MSS). We are collecting such samples from multiple transplant centers to address the following specific aims and close the following knowledge gaps: (1) Validate our novel observation that PTLD tissue positivity by MSS for anellovirus (and confirmed by PCR) serves as a biomarker for higher transplant recipient mortality after the diagnosis of PTLD; (2) determine the role of other oncogenic viruses in EBV-negative PTLD by unbiased MSS of multiple viral groupings, confirmed by other techniques; and (3) develop the necessary computational, algorithmic and software analytic tools required to determine association of EBV genome variants with worse presentations or outcomes in PTLD. Study completion will contribute to better patient care and may provide avenues for novel therapies.

  View details for DOI 10.1097/TXD.0000000000001723

  View details for PubMedID 39473523

  View details for PubMedCentralID PMC11521023

• Post-Transplant Lymphoproliferative Disorders (Review for Seminars in Nephrology). Seminars in nephrology Dharnidharka, V. R., Ruzinova, M. B., Marks, L. J. 2024: 151503

  Abstract

  Post-transplant lymphoproliferative disorders (PTLDs) are a heterogenous set of unregulated lymphoid cell proliferations after organ or tissue transplant. A majority of cases are associated with the Epstein-Barr virus and higher intensity of pharmacologic immunosuppression. The clinical presentations are numerous. The diagnosis is ideally by histology, except in cases where the tumor is inaccessible to biopsy. While some pre-emptive therapies and treatment strategies are available have reasonable success are available, they do not eliminate the high morbidity and significant mortality after PTLD.

  View details for DOI 10.1016/j.semnephrol.2024.151503

  View details for PubMedID 38519279

• Distinct Hodgkin lymphoma subtypes defined by noninvasive genomic profiling. Nature Alig, S. K., Esfahani, M. S., Garofalo, A., Li, M. Y., Rossi, C., Flerlage, T., Flerlage, J. E., Adams, R., Binkley, M. S., Shukla, N., Jin, M. C., Olsen, M., Telenius, A., Mutter, J. A., Schroers-Martin, J. G., Sworder, B. J., Rai, S., King, D. A., Schultz, A., Bögeholz, J., Su, S., Kathuria, K. R., Liu, C. L., Kang, X., Strohband, M. J., Langfitt, D., Pobre-Piza, K. F., Surman, S., Tian, F., Spina, V., Tousseyn, T., Buedts, L., Hoppe, R., Natkunam, Y., Fornecker, L. M., Castellino, S. M., Advani, R., Rossi, D., Lynch, R., Ghesquières, H., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., André, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. 2023

  Abstract

  The scarcity of malignant Hodgkin and Reed-Sternberg (HRS) cells hamper tissue-based comprehensive genomic profiling of classic Hodgkin lymphoma (cHL). Liquid biopsies, in contrast, show promise for molecular profiling of cHL due to relatively high circulating tumor DNA (ctDNA) levels1-4. Here, we show that the plasma representation of mutations exceeds the bulk tumor representation in most cases, making cHL particularly amenable to noninvasive profiling. Leveraging single-cell transcriptional profiles of cHL tumors, we demonstrate HRS ctDNA shedding to be shaped by DNASE1L3, whose increased tumor microenvironment-derived expression drives high ctDNA concentrations. Using this insight, we comprehensively profile 366 patients, revealing two distinct cHL genomic subtypes with characteristic clinical and prognostic correlates, as well as distinct transcriptional and immunological profiles. Furthermore, we identify a novel class of truncating IL4R-mutations that are dependent on IL13 signaling and therapeutically targetable with IL4R blocking antibodies. Finally, using PhasED-Seq5 we demonstrate the clinical value of pre- and on-treatment ctDNA levels for longitudinally refining cHL risk prediction, and for detection of radiographically occult minimal residual disease. Collectively, these results support the utility of noninvasive strategies for genotyping and dynamic monitoring of cHL as well as capturing molecularly distinct subtypes with diagnostic, prognostic, and therapeutic potential.

  View details for DOI 10.1038/s41586-023-06903-x

  View details for PubMedID 38081297

• Genomic, Transcriptional, and Immunological Validation of Distinct Molecular Subtypes of Classic Hodgkin Lymphoma through Tissue-Based and Noninvasive Methods Alig, S. K., Esfahani, M., Garofalo, A., Li, M., Rossi, C., Flerlage, T., Flerlage, J. E., Adams, R., Binkley, M. S., Shukla, N., Jin, M., Olsen, M., Telenius, A., Mutter, J. A., Schroers-Martin, J., Sworder, B. J., Rai, S., King, D., Schultz, A., Bogeholz, J., Su, S., Kathuria, K. R., Liu, C., Kang, X., Langfitt, D. M., Pobre-Piza, K., Tian, F., Strohband, M. J., Spina, V., Tousseyn, T., Buedts, L., Fornecker, L., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Ghesquieres, H., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-186810

  View details for Web of Science ID 001159306700178

• Performance of Positron Emission Tomography at Diagnosis and Response Assessment in Low and Intermediate-Risk Nodular Lymphocyte Predominant Hodgkin Lymphoma Marks, L. J., McCarten, K., Pei, Q., Wu, Y., Kelly, K. M., Schwartz, C., Wolden, S., Friedman, D. L., Castellino, S. M., Appel, B. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-179465

  View details for Web of Science ID 001159306706170

• Validation of Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event-Free Survival in Intermediate and High-Risk Hodgkin Lymphoma Marks, L. J., Zhou, Y., Zheng, Y., Feraco, A., Friedmann, A. M., Weinstein, H. J., Link, M. P., Flerlage, J. E. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-189991

  View details for Web of Science ID 001159740307197

• CURRENT STATE OF INTERNATIONAL HARMONIZATION EFFORTS FOR PEDIATRIC AND YOUNG ADULT HODGKIN LYMPHOMA: A REPORT FROM THE SEARCH FOR CAYAHL GROUP Seelisch, J., Punnett, A., Kelly, K., Mauz-Koerholz, C., Marks, L., Palese, M., Pabari, R., Dieckmann, K., Lai, H., Drachtman, R., Hoppe, B., Mccarten, K., Kluge, R., Kurch, L., Beishuizen, A., Stoevesandt, D., Flerlage, J. WILEY. 2023: S31-S32

  View details for Web of Science ID 001183650900056

• SUCCESSFUL INAUGURATION OF THE PEDIATRIC PTLD COLLABORATIVE (PPC) PROVIDES AN EXCELLENT PLATFORM FOR PTLD REGISTRY AND PROSPECTIVE STUDIES Afify, Z., Taj, M., Srivatsa, K., Edington, H., Miller, T., Dalal, M., Robles, J., Ford, J., Ehrhardt, M., Ureda, T., Rubinstein, J., Mccormack, S., Rivers, J., Chisholm, K., Kavanaugh, M., Bukowinski, A., Friehling, E., Alperstein, W., Pillai, P., Ford, M., Reddy, S., Marks, L., Smith, C., Mason, C., Orjuela-Grimm, M. WILEY. 2023

  View details for Web of Science ID 001183650901187

• Disease site number was not prognostic in a low-risk Hodgkin lymphoma combined modality trial: revisiting PHC HOD90. Blood advances Feraco, A. M., Zhou, Y., Zheng, Y., Marks, L. J., Friedmann, A. M., Weinstein, H. J., Link, M. P., Flerlage, J. E. 2023

  View details for DOI 10.1182/bloodadvances.2023010944

  View details for PubMedID 37647596

• POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE IN A PATIENT WITH SCHIMKE IMMUNO-OSSEOUS DYSPLASIA Rao, R., Grimm, P., Lewis, D., Spunt, S., Marks, L. WILEY. 2023: S75-S76

  View details for Web of Science ID 001042987300147

• Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis. Marks, L., Ritter, V., Schultz, L. M., Lowe, E. J., Aftandilian, C., Relapsed ALCL REAL Consortium LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for DOI 10.1200/JCO.2023.41.16_suppl.10032

  View details for Web of Science ID 001555455500022

• Outcomes in pediatric relapsed/refractory anaplastic large cell lymphoma: A multi-institutional retrospective analysis Marks, L., Ritter, V., Schultz, L. M., Lowe, E. J., Aftandilian, C., Relapsed ALCL Real Consortium LIPPINCOTT WILLIAMS & WILKINS. 2023

  View details for Web of Science ID 001053772002598

• Brentuximab Vedotin Following Autologous Transplantation in Pediatric Patients with Relapsed/Refractory Hodgkin Lymphoma. Blood advances Forlenza, C. J., Rosenzweig, J., Mauguen, A., Buhtoiarov, I. N., Cuglievan, B., Dave, H., Deyell, R., Flerlage, J. E., Franklin, A. R., Krajewski, J., Leger, K. J., Marks, L. J., Norris, R. E., Pacheco, M., Willen, F. K., Yan, A. P., Harker-Murray, P., Giulino-Roth, L. 2023

  Abstract

  Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with approximately 50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplant (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy following ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to adult patients. With a median follow up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory Hodgkin lymphoma.

  View details for DOI 10.1182/bloodadvances.2022009323

  View details for PubMedID 36897253

• Cellular and humoral immunotherapy in children, adolescents and young adults with non-Hodgkin lymphoma. Best practice & research. Clinical haematology Chu, Y., Gardenswartz, A., Diorio, C., Marks, L. J., Lowe, E., Teachey, D. T., Cairo, M. S. 2023; 36 (1): 101442

  Abstract

  The prognosis is dismal (2-year overall survival less than 25%) for childhood, adolescent, and young adult (CAYA) with relapsed and/or refractory (R/R) non-Hodgkin lymphoma (NHL). Novel targeted therapies are desperately needed for this poor-risk population. CD19, CD20, CD22, CD79a, CD38, CD30, LMP1 and LMP2 are attractive targets for immunotherapy in CAYA patients with R/R NHL. Novel anti-CD20 monoclonal antibodies, anti-CD38 monoclonal antibody, antibody drug conjugates and T and natural killer (NK)-cell bispecific and trispecific engagers are being investigated in the R/R setting and are changing the landscape of NHL therapy. A variety of cellular immunotherapies such as viral activated cytotoxic T-lymphocyte, chimeric antigen receptor (CAR) T-cells, NK and CAR NK-cells have been investigated and provide alternative options for CAYA patients with R/R NHL. Here, we provide an update and clinical practice guidance of utilizing these cellular and humoral immunotherapies in CAYA patients with R/R NHL.

  View details for DOI 10.1016/j.beha.2023.101442

  View details for PubMedID 36907635

• Multicenter study of pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders. Cancer Afify, Z. A., Taj, M. M., Orjuela-Grimm, M., Srivatsa, K., Miller, T. P., Edington, H. J., Dalal, M., Robles, J., Ford, J. B., Ehrhardt, M. J., Ureda, T. J., Rubinstein, J. D., McCormack, S., Rivers, J. M., Chisholm, K. M., Kavanaugh, M. K., Bukowinski, A. J., Friehling, E. D., Ford, M. C., Reddy, S. N., Marks, L. J., Smith, C. M., Mason, C. C. 2022

  Abstract

  BACKGROUND: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorder [EBV(-)M-PTLD] comprises approximately 10% of M-PTLD. No large multi-institutional pediatric-specific reports on treatment and outcome are available.METHODS: A multi-institutional retrospective review of solid organ recipients diagnosed with EBV(-)M-PTLD aged ≤21years between 2001 and 2020 in 12 centers in the United States and United Kingdom was performed, including demographics, staging, treatment, and outcomes data.RESULTS: Thirty-six patients were identified with EBV(-)M-PTLD. Twenty-three (63.9%) were male. Median age (range) at transplantation, diagnosis of EBV(-)M-PTLD, and interval from transplant to PTLD were 2.2 years (0.1-17), 14 years (3.0-20), and 8.5 years (0.6-18.3), respectively. Kidney (n=17 [47.2%]) and heart (n=13 [36.1%]) were the most commonly transplanted organs. Most were Murphy stage III (n=25 [69.4%]). Lactate dehydrogenase was elevated in 22/34 (64.7%) and ≥2 times upper limit of normal in 11/34 (32.4%). Pathological diagnoses included diffuse large B-cell lymphoma (n=31 [86.1%]) and B-non-Hodgkin lymphoma (B-NHL) not otherwise specified (NOS) (n=5 [13.9%]). Of nine different regimens used, the most common were: pediatric mature B-NHL-specific regimen (n=13 [36.1%]) and low-dose cyclophosphamide, prednisone, and rituximab (n=9 [25%]). Median follow-up from diagnosis was 3.0 years (0.3-11.0 years). Three-year event-free survival (EFS) and overall survival (OS) were 64.8% and 79.9%, respectively. Of the seven deaths, six were from progressive disease.CONCLUSIONS: EFS and OS were comparable to pediatric EBV(+) PTLD, but inferior to mature B-NHL in immunocompetent pediatric patients. The wide range of therapeutic regimens used directs our work toward developing an active multi-institutional registry to design prospective studies.PLAIN LANGUAGE SUMMARY: Pediatric Epstein-Barr virus-negative monomorphic post solid organ transplant lymphoproliferative disorders (EBV(-)M-PTLD) have comparable outcomes to EBV(+) PTLD, but are inferior to diffuse large B-cell lymphoma in immunocompetent pediatric patients. The variety of treatment regimens used highlights the need to develop a pediatric PTLD registry to prospectively evaluate outcomes. The impact of treatment regimen on relapse risk could not be assessed because of small numbers. In the intensive pediatric B-non-Hodgkin lymphoma chemoimmunotherapy group, 11 of 13 patients remain alive in complete remission after 0.6 to 11years.

  View details for DOI 10.1002/cncr.34600

  View details for PubMedID 36571557

• Burkitt lymphoma after solid-organ transplant: Treatment and outcomes in the paediatric PTLD collaborative. British journal of haematology Afify, Z., Orjuela-Grimm, M., Smith, C. M., Dalal, M., Ford, J. B., Pillai, P., Robles, J. M., Reddy, S., McCormack, S., Ehrhardt, M. J., Ureda, T., Alperstein, W., Edington, H., Miller, T. P., Rubinstein, J. D., Kavanaugh, M., Bukowinski, A. J., Friehling, E., Rivers, J. M., Chisholm, K. M., Marks, L. J., Mason, C. C. 2022

  Abstract

  Burkitt lymphoma arising in paediatric post-solid-organ transplantation-Burkitt lymphoma (PSOT-BL) is a clinically aggressive malignancy and a rare form of post-transplant lymphoproliferative disorder (PTLD). We evaluated 35 patients diagnosed with PSOT-BL at 14 paediatric medical centres in the United States. Median age at organ transplantation was 2.0 years (range: 0.1-14) and age at PSOT-BL diagnosis was 8.0 years (range: 1-17). All but one patient had late onset of PSOT-BL (≥2 years post-transplant), with a median interval from transplant to PSOT-BL diagnosis of 4.0 years (range: 0.4-12). Heart (n = 18 [51.4%]) and liver (n = 13 [37.1%]) were the most frequently transplanted organs. No patients had loss of graft or treatment-related mortality. A variety of treatment regimens were used, led by intensive Burkitt lymphoma-specific French-American-British/Lymphomes Malins B (FAB/LMB), n = 13 (37.1%), and a low-intensity regimen consisting of cyclophosphamide, prednisone and rituximab (CPR) n = 12 (34.3%). Median follow-up was 6.7 years (range: 0.5-17). Three-year event-free and overall survival were 66.2% and 88.0%, respectively. Outcomes of PSOT-BL patients receiving BL-specific intensive regimens are comparable to reported BL outcomes in immunocompetent children. Multi-institutional collaboration is feasible and provides the basis of prospective data collection to determine the optimal treatment regimen for PSOT-BL.

  View details for DOI 10.1111/bjh.18498

  View details for PubMedID 36454546

• Development of clinical pathways to improve multidisciplinary care of high-risk pediatric oncology patients. Frontiers in oncology Reschke, A., Richards, R. M., Smith, S. M., Long, A. H., Marks, L. J., Schultz, L., Kamens, J. L., Aftandilian, C., Davis, K. L., Gruber, T., Sakamoto, K. M. 2022; 12: 1033993

  Abstract

  Clinical pathways are evidence-based tools that have been integrated into many aspects of pediatric hospital medicine and have proven effective at reducing in-hospital complications from a variety of diseases. Adaptation of similar tools for specific, high-risk patient populations in pediatric oncology has been slower, in part due to patient complexities and variations in management strategies. There are few published studies of clinical pathways for pediatric oncology patients. Pediatric patients with a new diagnosis of leukemia or lymphoma often present with one or more "oncologic emergencies" that require urgent intervention and deliberate multidisciplinary care to prevent significant consequences. Here, we present two clinical pathways that have recently been developed using a multidisciplinary approach at a single institution, intended for the care of patients who present with hyperleukocytosis or an anterior mediastinal mass. These clinical care pathways have provided a critical framework for the immediate care of these patients who are often admitted to the pediatric intensive care unit for initial management. The goal of the pathways is to facilitate multidisciplinary collaborations, expedite diagnosis, and streamline timely treatment initiation. Standardizing the care of high-risk pediatric oncology patients will ultimately decrease morbidity and mortality associated with these diseases to increase the potential for excellent outcomes.

  View details for DOI 10.3389/fonc.2022.1033993

  View details for PubMedID 36523979

  View details for PubMedCentralID PMC9744920

• Viral cfDNA Profiling Reveals Distinct EBV Subtypes and Stratifies Risk in Hodgkin Lymphomas Garofalo, A., Alig, S. K., Schroers-Martin, J., Shyam, R., Olsen, M., Kurtz, D. M., Rossi, C., Schultz, A., Kathuria, K. R., Liu, C., Spina, V., Flerlage, J. E., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Casasnovas, O., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1318-1319

  View details for DOI 10.1182/blood-2022-159230

  View details for Web of Science ID 000893223201135

• End of Treatment Positron Emission Tomography Response and Outcomes in Post-Transplant Lymphoproliferative Disorder Marks, L. J., Green, M., Agarwal, M., Goss, C., Storch, G., Gratzinger, D., Dharnidharka, V. AMER SOC HEMATOLOGY. 2022: 9559-9560

  View details for DOI 10.1182/blood-2022-165443

  View details for Web of Science ID 000893230302246

• Distinct Molecular Subtypes of Classic Hodgkin Lymphoma Identified By Comprehensive Noninvasive Profiling Alig, S. K., Esfahani, M., Li, M. Y., Adams, R., Garofalo, A., Jin, M. C., Olsen, M., Telenius, A., Sworder, B., Schroers-Martin, J., King, D. A., Rossi, C., Schultz, A., Kathuria, K. R., Liu, C., Spina, V., Buedts, L., Flerlage, J. E., Castellino, S. M., Advani, R. H., Rossi, D., Lynch, R. C., Casasnovas, O., Kurtz, D. M., Marks, L. J., Link, M. P., Andre, M., Vandenberghe, P., Steidl, C., Diehn, M., Alizadeh, A. A. AMER SOC HEMATOLOGY. 2022: 1295-1296

  View details for DOI 10.1182/blood-2022-164744

  View details for Web of Science ID 000893223201127

• TREATMENT OF POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER (PTLD): A MULTI-CENTER PEDIATRIC SERIES Marks, L., Green, M., Storch, G., Gratzinger, D., Gu, H., Goss, C., Dharnidharka, V. WILEY. 2022

  View details for Web of Science ID 000859203900049

• Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors. Med (New York, N.Y.) Coutinho, D. F., Mundi, P. S., Marks, L. J., Burke, C., Ortiz, M. V., Diolaiti, D., Bird, L., Vallance, K. L., Ibáñez, G., You, D., Long, M., Rosales, N., Grunn, A., Ndengu, A., Siddiquee, A., Gaviria, E. S., Rainey, A. R., Fazlollahi, L., Hosoi, H., Califano, A., Kung, A. L., Dela Cruz, F. S. 2022

  Abstract

  Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. In vitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. In vivo anti-tumor activity was assessed in patient-derived xenograft (PDX) models of MRTs and WTs.metaVIPER analysis identified markedly aberrant activation of XPO1 in MRTs and WTs compared with other tumor types. All MRT and most WT cell lines demonstrated baseline, aberrant XPO1 activity with in vitro sensitivity to selinexor via cell-cycle arrest and induction of apoptosis. In vivo, XPO1 inhibitors significantly abrogated tumor growth in PDX models, inducing effective disease control with sustained treatment. Corroborating human relevance, we present a case report of a child with multiply relapsed WTs with prolonged disease control on selinexor.We report on a novel systems-biology-based comparative framework to identify non-genetically encoded vulnerabilities in genomically quiescent pediatric cancers. These results have provided preclinical rationale for investigation of XPO1 inhibitors in an upcoming investigator-initiated clinical trial of selinexor in children with MRTs and WTs and offer opportunities for exploration of inferred XPO1 activity as a potential predictive biomarker for response.This work was funded by CureSearch for Children's Cancer, Alan B. Slifka Foundation, NIH (U01 CA217858, S10 OD012351, and S10 OD021764), Michael's Miracle Cure, Hyundai Hope on Wheels, Cannonball Kids Cancer, Conquer Cancer the ASCO Foundation, Cycle for Survival, Paulie Strong Foundation, and the Grayson Fund.

  View details for DOI 10.1016/j.medj.2022.09.002

  View details for PubMedID 36195086

• Targeting of the nuclear export protein XPO1 represents a non-genetically encoded vulnerability in malignant rhabdoid and Wilms tumors Coutinho, D. F., Burke, C., Mundi, P., Ortiz, M. V., Vallance, K. L., Long, M., Rosales, N., Ibanez, G., Marks, L. J., Diolaiti, D., Ndengu, A., You, D., Siddiquee, A., Gaviria, E. S., Rainey, A. R., Califano, A., Kung, A. L., Dela Cruz, F. S. AMER ASSOC CANCER RESEARCH. 2022

  View details for Web of Science ID 000892509505490

• Pediatric EBV-negative monomorphic post-solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers. Afify, Z. A. M., Taj, M., Srivatsa, K., Miller, T. P., Edington, H., Dalal, M., Robles, J., Ford, J., Ehrhardt, M. J., Ureda, T., Rubinstein, J., McCormack, S., Rivers, J. M., Chisholm, K. M., Kavanaugh, M., Bukowinski, A. J., Friehling, E., Marks, L., Smith, C., Mason, C. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300015

• Early presentation of post-transplant lymphoproliferative disorders (PTLD) or tumor positivity for epstein-barr virus does not confer better patient survival: A multicenter pediatric series Green, M., Marks, L., Storch, G. A., Dharnidharka, V. R., PTLD MSMS Grp WILEY. 2022

  View details for Web of Science ID 000783167500151

• Practice patterns for the management of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL): an international survey by the Global NLPHL One Working Group (GLOW). Leukemia & lymphoma Lo, A. C., Major, A., Super, L., Appel, B., Shankar, A., Constine, L. S., Marks, L. J., Kelly, K. M., Metzger, M. L., Buhtoiarov, I. N., Mauz-Korholz, C., Costa, A. R., Binkley, M. S., Flerlage, J. 2022: 1-4

  View details for DOI 10.1080/10428194.2022.2053533

  View details for PubMedID 35357263

• Pediatric Aggressive Mature B-Cell Lymphomas, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Barth, M., Xavier, A. C., Armenian, S., Audino, A. N., Blazin, L., Bloom, D., Chung, J., Davies, K., Ding, H., Ford, J. B., Galardy, P. J., Hanna, R., Hayashi, R., Lee-Miller, C., Machnitz, A. J., Maloney, K. W., Marks, L., Martin, P. L., McCall, D., Pacheco, M., Reilly, A. F., Roshal, M., Song, S., Weinstein, J., Zarnegar-Lumley, S., McMillian, N., Schonfeld, R., Sundar, H. 2022; 20 (11): 1267-1275

  Abstract

  NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pediatric Aggressive Mature B-Cell Lymphomas include recommendations for the diagnosis and management of pediatric patients with primary mediastinal large B-cell lymphoma (PMBL) and sporadic variants of Burkitt lymphoma and diffuse large B-cell lymphoma. PMBL is now considered as a distinct entity arising from mature thymic B-cells accounting for 2% of mature B-cell lymphomas in children and adolescents. This discussion section includes the recommendations outlined in the NCCN Guidelines for the diagnosis and management of pediatric patients with PMBL.

  View details for DOI 10.6004/jnccn.2022.0057

  View details for PubMedID 36351334

• Brentuximab Vedotin As Consolidation Therapy Following Autologous Stem Cell Transplantation in Children and Adolescents with Relapsed/Refractory Hodgkin Lymphoma: A Multi-Center Retrospective Analysis Forlenza, C. J., Rosenzweig, J., Mauguen, A., Buhtoiarov, I., Cuglievan, B., Dave, H., Deyell, R. J., Flerlage, J., Franklin, A., Krajewski, J., Leger, K. J., Marks, L., Norris, R., Pacheco, M., Willen, F., Yan, A., Harker-Murray, P., Roth, L. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-151808

  View details for Web of Science ID 000736413901194

• Outcome of Post Solid Organ Transplant Burkitt Lymphoma (PSOT-BL): A Report from the Pediatric PTLD Collaborative (PPC) Afify, Z., Orjuela, M., Smith, C., Dalal, M., Ford, J. B., Pillai, P., Robles, J., Reddy, S., McCormack, S., Ehrhardt, M. J., Ureda, T., Edington, H., Miller, T. P., Rubinstein, J., Marks, L., Mason, C. C. AMER SOC HEMATOLOGY. 2021

  View details for DOI 10.1182/blood-2021-149033

  View details for Web of Science ID 000736413902015

• Improving Risk Stratification to Guide Treatment Decisions for Children, Adolescents, and Young Adults With Hodgkin Lymphoma JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Marks, L. J. 2021; 19 (6): 666-668

  View details for DOI 10.6004/jnccn.2021.7041

  View details for Web of Science ID 000672859700004

  View details for PubMedID 34214966

• Expert consensus statements for Waldeyer's ring involvement in pediatric Hodgkin lymphoma: The staging, evaluation, and response criteria harmonization (SEARCH) for childhood, adolescent, and young adult Hodgkin lymphoma (CAYAHL) group. Pediatric blood & cancer Seelisch, J. n., De Alarcon, P. A., Flerlage, J. E., Hoppe, B. S., Kaste, S. C., Kelly, K. M., Kurch, L. n., Marks, L. J., Mauz-Koerholz, C. n., McCarten, K. n., Metzger, M. L., Stroevesandt, D. n., Voss, S. D., Punnett, A. n. 2020: e28361

  Abstract

  Waldeyer's ring (WR) involvement in pediatric Hodgkin lymphoma (HL) is extremely rare and criteria for determining involvement and response to treatment are unclear. The international Staging, Evaluation, and Response Criteria Harmonization for Childhood, Adolescent and Young Adult Hodgkin Lymphoma (SEARCH for CAYAHL) Group performed a systematic review of the literature in search of involvement or response criteria, or evidence to support specific criteria. Only 166 cases of HL with WR involvement were reported in the literature, 7 of which were pediatric. To date no standardized diagnostic or response assessment criteria are available. Given the paucity of evidence, using a modified Delphi survey technique, expert consensus statements were developed by the SEARCH group to allow for a more consistent definition of disease and response evaluation related to this rare site of involvement among pediatric oncologists. The available evidence and expert consensus statements are summarized.

  View details for DOI 10.1002/pbc.28361

  View details for PubMedID 32672879

• Pediatric Aggressive Mature B-Cell Lymphomas, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network : JNCCN Davies, K., Barth, M., Armenian, S., Audino, A. N., Barnette, P., Cuglievan, B., Ding, H., Ford, J. B., Galardy, P. J., Gardner, R., Hanna, R., Hayashi, R., Kovach, A. E., Machnitz, A. J., Maloney, K. W., Marks, L., Page, K., Reilly, A. F., Weinstein, J. L., Xavier, A. C., McMillian, N. R., Freedman-Cass, D. A. 2020; 18 (8): 1105–23

  Abstract

  Pediatric aggressive mature B-cell lymphomas are the most common types of non-Hodgkin lymphoma in children, and they include Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). These diseases are highly aggressive but curable, the treatment is complex, and patients may have many complicated supportive care issues. The NCCN Guidelines for Pediatric Aggressive Mature B-Cell Lymphomas provide guidance regarding pathology and diagnosis, staging, initial treatment, disease reassessment, surveillance, therapy for relapsed/refractory disease, and supportive care for clinicians who treat sporadic pediatric BL and DLBCL.

  View details for DOI 10.6004/jnccn.2020.0036

  View details for PubMedID 32755986

• Brentuximab Vedotin as Consolidation Therapy After Autologous Stem Cell Transplantation in Children and Adolescents (<18y) With Early Relapse Hodgkin Lymphoma. Journal of pediatric hematology/oncology Fernandez, K. S., Mavers, M., Marks, L. J., Agarwal, R. 2019

  Abstract

  We describe 6 pediatric patients (12 to 18y) with relapsed or refractory Hodgkin lymphoma treated with consolidative Brentuximab vedotin (Bv) following reinduction chemotherapy and autologous stem cell transplantation. The progression-free survival after autologous stem cell transplantation was 12, 18, 22, 24, 30, and 30 months. Most patients tolerated Bv well although 2 patients developed grade 3 neuropathy that prevent them from completing the scheduled 16 doses of Bv. Consolidative Bv in children and adolescents, as currently recommended for adult patients with early relapsed or refractory Hodgkin lymphoma, is feasible but with some significant toxicities.

  View details for DOI 10.1097/MPH.0000000000001703

  View details for PubMedID 31876780

• Outcomes in intermediate-risk pediatric lymphocyte-predominant Hodgkin lymphoma: A report from the Children's Oncology Group. Pediatric blood & cancer Marks, L. J., Pei, Q., Bush, R., Buxton, A., Appel, B., Kelly, K. M., Schwartz, C. L., Friedman, D. L. 2018; 65 (12): e27375

  Abstract

  Optimal management of patients with intermediate-risk lymphocyte-predominant Hodgkin lymphoma (LPHL) is unclear due to their small numbers in most clinical trials. Children's Oncology Group AHOD0031, a randomized phase III trial of pediatric patients with intermediate-risk Hodgkin lymphoma (HL), included patients with LPHL. We report the outcomes of these patients and present directions for future therapeutic strategies.Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) followed by response evaluation. Slow early responders were randomized to two additional ABVE-PC cycles ± two dexamethasone, etoposide, cisplatin, and cytarabine cycles and all received involved field radiotherapy (IFRT). Rapid early responders (RERs) received two additional ABVE-PC cycles. RERs with complete response (CR) were randomized to IFRT or no further therapy. RERs without CR received IFRT.Ninety-six (5.6%) of 1711 patients on AHOD0031 had LPHL. Patients with LPHL were more likely to achieve RER (93.6% vs. 81.0%; P = 0.002) and CR (74.2% vs. 49.3%; P = 0.000005) following chemotherapy compared with patients with classical HL. Five-year event-free survival (EFS) was superior in patients with LPHL (92.2%) versus classical HL (83.5%) (P = 0.04), without difference in overall survival (OS). Among RERs with CR following chemotherapy (n = 33), there was no difference in EFS or OS between those randomized to receive or not receive IFRT.Children and adolescents with intermediate-risk LPHL represent ideal candidates for response-adapted therapy based on their favorable outcomes. The majority of patients treated with the ABVE-PC backbone achieve RER with CR status and can be treated successfully without IFRT.

  View details for DOI 10.1002/pbc.27375

  View details for PubMedID 30277639

  View details for PubMedCentralID PMC6192844

• Pericardial effusion in Hodgkin lymphoma: a report from the Children's Oncology Group AHOD0031 protocol BLOOD Marks, L. J., McCarten, K. M., Pei, Q., Friedman, D. L., Schwartz, C. L., Kelly, K. M. 2018; 132 (11): 1208–11

  View details for DOI 10.1182/blood-2018-02-834465

  View details for Web of Science ID 000444425900016

  View details for PubMedID 30061157

  View details for PubMedCentralID PMC6137557

• Stroke Prevalence in Children With Sickle Cell Disease in Sub-Saharan Africa: A Systematic Review and Meta-Analysis. Global pediatric health Marks, L. J., Munube, D., Kasirye, P., Mupere, E., Jin, Z., LaRussa, P., Idro, R., Green, N. S. 2018; 5: 2333794X18774970

  Abstract

  Objectives. The prevalence of stroke among children with sickle cell disease (SCD) in sub-Saharan Africa was systematically reviewed. Methods. Comprehensive searches of PubMed, Embase, and Web of Science were performed for articles published between 1980 and 2016 (English or French) reporting stroke prevalence. Using preselected inclusion criteria, titles and abstracts were screened and full-text articles were reviewed. Results. Ten full-text articles met selection criteria. Cross-sectional clinic-based data reported 2.9% to 16.9% stroke prevalence among children with SCD. Using available sickle gene frequencies by country, estimated pediatric mortality, and fixed- and random-effects model, the number of affected individuals is projected as 29 800 (95% confidence interval = 25 571-34 027) and 59 732 (37 004-82 460), respectively. Conclusion. Systematic review enabled the estimation of the number of children with SCD stroke in sub-Saharan Africa. High disease mortality, inaccurate diagnosis, and regional variability of risk hamper more precise estimates. Adopting standardized stroke assessments may provide more accurate determination of numbers affected to inform preventive interventions.

  View details for DOI 10.1177/2333794X18774970

  View details for PubMedID 29785408

  View details for PubMedCentralID PMC5954575

• Precision Medicine in Children and Young Adults with Hematologic Malignancies and Blood Disorders: The Columbia University Experience FRONTIERS IN PEDIATRICS Marks, L. J., Oberg, J. A., Pendrick, D., Sireci, A. N., Glasser, C., Coval, C., Zylber, R. J., Chung, W. K., Pang, J., Turk, A. T., Hsiao, S. J., Mansukhani, M. M., Bender, J., Kung, A. L., Sulis, M. 2017; 5: 265

  Abstract

  The advent of comprehensive genomic profiling has markedly advanced the understanding of the biology of pediatric hematological malignancies, however, its application to clinical care is still unclear. We present our experience integrating genomic data into the clinical management of children with high-risk hematologic malignancies and blood disorders and describe the broad impact that genomic profiling has in multiple aspects of patient care.The Precision in Pediatric Sequencing Program at Columbia University Medical Center instituted prospective clinical next-generation sequencing (NGS) for high-risk malignancies and blood disorders. Testing included cancer whole exome sequencing (WES) of matched tumor-normal samples or targeted sequencing of 467 cancer-associated genes, when sample adequacy was a concern, and tumor transcriptome (RNA-seq). A multidisciplinary molecular tumor board conducted interpretation of results and final tiered reports were transmitted to the electronic medical record according to patient preferences.Sixty-nine samples from 56 patients with high-risk hematologic malignancies and blood disorders were sequenced. Patients carried diagnoses of myeloid malignancy (n = 25), lymphoid malignancy (n = 25), or histiocytic disorder (n = 6). Six patients had only constitutional WES, performed for a suspicion of an inherited predisposition for their disease. For the remaining 50 patients, tumor was sequenced with matched normal tissue when available. The mean number of somatic variants per sample was low across the different disease categories (2.85 variants/sample). Interestingly, a gene fusion was identified by RNA-seq in 58% of samples who had adequate RNA available for testing. Molecular profiling of tumor tissue led to clinically impactful findings in 90% of patients. Forty patients (80%) had at least one targetable gene variant or fusion identified in their tumor tissue; however, only seven received targeted therapy. Importantly, NGS findings contributed to the refinement of diagnosis and prognosis for 34% of patients. Known or likely pathogenic germline alterations were discovered in 24% of patients involving cancer predisposition genes in 12% of cases.Incorporating whole exome and transcriptome profiling of tumor and normal tissue into clinical practice is feasible, and the value that comprehensive testing provides extends beyond the ability to target-specific mutations.

  View details for DOI 10.3389/fped.2017.00265

  View details for Web of Science ID 000417730800001

  View details for PubMedID 29312904

  View details for PubMedCentralID PMC5732960