All Publications

  • Phase 1b/2 Trial of Enasidenib in Lower-Risk MDS and Nonproliferative CMML without Isocitrate Dehydrogenase Type 2 Mutations Kuo, E., Santiago, V., Tanaka, K., Puram, V., Zhou, C., Tai, J. W., Mannis, G., Majeti, R., Zhang, T. Y. AMER SOC HEMATOLOGY. 2023

    View details for DOI 10.1182/blood-2023-187644

    View details for Web of Science ID 001159306707106

  • Older Adults With Newly Diagnosed AML: Hot Topics for the Practicing Clinician. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting Lai, C., Bhansali, R. S., Kuo, E. J., Mannis, G., Lin, R. J. 2023; 43: e390018

    Abstract

    Over the past decade, our understanding of AML pathogenesis and pathophysiology has improved significantly with mutational profiling. This has led to translational advances in therapeutic options, as there have been 10 new US Food and Drug Administration (FDA) approvals for AML therapies since 2017, half of which target specific driver mutations in FLT3, IDH1, or IDH2. These new agents have expanded the therapeutic armamentarium for AML, particularly for patients who are considered ineligible for intensive chemotherapy with anthracycline- and cytarabine-containing regimens. These new treatment options are relevant because the median age at diagnosis is 68 years, and outcomes for patients older than 60 years have historically been dismal. However, the optimal approach to incorporating novel agents into frontline regimens remains a clinical challenge, particularly with regard to sequencing of therapies, considering the role of allogeneic hematopoietic stem cell transplantation and managing toxicities.

    View details for DOI 10.1200/EDBK_390018

    View details for PubMedID 37155946

  • Neurotoxicity with blinatumomab in combination with intrathecal methotrexate therapy. Leukemia & lymphoma On, S., Kuo, E., Lau, K. M. 2022: 1-4

    View details for DOI 10.1080/10428194.2022.2136949

    View details for PubMedID 36318866

  • 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

  • Real-World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated With Inotuzumab Ozogamicin. Clinical lymphoma, myeloma & leukemia Badar, T., Szabo, A., Wadleigh, M., Liedtke, M., Arslan, S., Siebenaller, C., Aldoss, I., Schultz, E., Hefazi, M., Litzow, M. R., Kuo, E., Wang, A., Curran, E., Shallis, R. M., Podoltsev, N., Balasubramanian, S., Yang, J., Mattison, R., Burkart, M., Dinner, S., Advani, A., Atallah, E. 2020

    Abstract

    BACKGROUND: Inotuzumab ozogamicin (InO) is an anti-CD22 monoclonal antibody-drug (calicheamicin) conjugate that has shown superior efficacy compared to conventional chemotherapy in relapsed/refractory (RR) B-cell acute lymphocytic leukemia (ALL) patients. We sought to find the safety and efficacy of InO in a real-world setting.PATIENTS AND METHODS: A multicenter cohort analysis on 84 RR ALL patients who received InO outside of clinical trials was conducted to evaluate response and toxicity.RESULTS: The median (range) age of patients at InO initiation was 50 (20-87) years. Forty patients (48%) had≥ 3 therapies and 23 patients (27%) underwent allogeneic hematopoietic stem-cell transplantation (allo-HCT) before InO. The median (range) number of cycles of InO provided was 2 (1-6), and cumulative dose was 3.3 (1.8-9.3) mg/m2. Overall response rate (complete remission/complete remission with incomplete count recovery) was 63%; 44% had complete remission with minimal residual disease negativity. Twenty-three patients (27%) with response received allo-HCT. The median duration of response was 11.5 months and when censored at allo-HCT was not reached (51% in remission at 2 years). The median overall survival after InO was 11.6 months and when censored at time of allo-HCT was 13.6 months. The most common grade 3 or higher adverse events observed were transaminitis (16%), hyperbilirubinemia (5%), bleeding (4%), veno-occlusive disease (2%), and hyperglycemia (2%). In multivariate analysis, allo-HCT after InO did not retain favorable significance for duration of response (hazard ratio= 1.27; 95% confidence interval, 0.89-1.61; P= .2) or overall survival (hazard ratio= 1.10; 95% confidence interval, 0.37-3.25; P= .85).CONCLUSION: InO was well tolerated and had significant efficacy in RR B-cell ALL patients.

    View details for DOI 10.1016/j.clml.2020.03.004

    View details for PubMedID 32291234

  • Clinical Outcome with Allogeneic Hematopoietic Stem Cell Transplantation after Blinatumomab or Inotuzumab Ozogamicin in Patients with B-Cell Acute Lymphoblastic Leukemia: Real World Experience Badar, T., Advani, A. S., Liedtke, M., Arslan, S., Khan, M., Aldoss, I., Sienbenaller, C., Schultz, E., Hefazi, M., Shallis, R., Yurkiewicz, I., Podoltsev, N., Patel, A., Curran, E., Kuo, E., Wang, A., Balasubramanian, S., Yang, J., Mattison, R., Burkart, M., Dinner, S., Litzow, M. R., Wadleigh, M., Atallah, E. ELSEVIER SCIENCE INC. 2020: S101–S102

    View details for Web of Science ID 000516887900137

  • Sequencing of novel agents in relapsed/refractory B-cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia. Cancer Badar, T. n., Szabo, A. n., Dinner, S. n., Liedtke, M. n., Burkart, M. n., Shallis, R. M., Yurkiewicz, I. R., Kuo, E. n., Khan, M. A., Balasubramanian, S. n., Yang, J. n., Hefazi, M. n., Podoltsev, N. n., Patel, A. n., Curran, E. n., Wang, A. n., Arslan, S. n., Aldoss, I. n., Siebenaller, C. n., Mattison, R. J., Litzow, M. R., Wadleigh, M. n., Advani, A. S., Atallah, E. n. 2020

    Abstract

    The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity.In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared.Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09).Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.

    View details for DOI 10.1002/cncr.33340

    View details for PubMedID 33259056

  • Real World Outcomes of Adult B-Cell Acute Lymphocytic Leukemia Patients Treated with Inotuzumab Ozogamicin Badar, T., Szabo, A., Wadleigh, M., Liedtke, M., Arslan, S., Siebenaller, C., Aldoss, I., Schultz, E., Hefazi, M., Litzow, M., Kuo, E., Wang, A., Curran, E. K., Shallis, R. M., Podoltsev, N. A., Balasubramanian, S., Yang, J., Mattison, R. J., Burkart, M., Dinner, S., Advani, A. S., Atallah, E. L. AMER SOC HEMATOLOGY. 2019

    View details for DOI 10.1182/blood-2019-124882

    View details for Web of Science ID 000577160401118

  • KRAS (but not BRAF) mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma JOURNAL OF PATHOLOGY Tsang, Y. T., Deavers, M. T., Sun, C. C., Kwan, S., Kuo, E., Malpica, A., Mok, S. C., Gershenson, D. M., Wong, K. 2013; 231 (4): 449-456

    Abstract

    BRAF and KRAS mutations in ovarian serous borderline tumours (OSBTs) and ovarian low-grade serous carcinomas (LGSCs) have been previously described. However, whether those OSBTs would progress to LGSCs or whether those LGSCs were developed from OSBT precursors in previous studies is unknown. Therefore, we assessed KRAS and BRAF mutations in tumour samples from 23 recurrent LGSC patients with a known initial diagnosis of OSBT. Paraffin blocks from both OSBT and LGSC samples were available for five patients, and either OSBTs or LGSCs were available for another 18 patients. Tumour cells from paraffin-embedded tissues were dissected out for mutation analysis by conventional polymerase chain reaction (PCR) and Sanger sequencing. Tumours that appeared to have wild-type KRAS by conventional PCR-Sanger sequencing were further analysed by full COLD (co-amplification at lower denaturation temperature)-PCR and deep sequencing. Full COLD-PCR was able to enrich the amplification of mutated alleles. Deep sequencing was performed with the Ion Torrent personal genome machine (PGM). By conventional PCR-Sanger sequencing, BRAF mutation was detected only in one patient and KRAS mutations were detected in ten patients. Full COLD-PCR deep sequencing detected low-abundance KRAS mutations in eight additional patients. Three of the five patients with both OSBT and LGSC samples available had the same KRAS mutations detected in both OSBT and LGSC samples. The remaining two patients had only KRAS mutations detected in their LGSC samples. For patients with either OSBT or LGSC samples available, KRAS mutations were detected in seven OSBT samples and six LGSC samples. Surprisingly, patients with the KRAS G12V mutation have shorter survival times. In summary, KRAS mutations are very common in recurrent LGSC, while BRAF mutations are rare. The findings indicate that recurrent LGSC can arise from proliferation of OSBT tumour cells with or without detectable KRAS mutations.

    View details for DOI 10.1002/path.4252

    View details for Web of Science ID 000326960100007

    View details for PubMedID 24549645

    View details for PubMedCentralID PMC4095747