Allogeneic Hematopoietic Cell Transplantation for Acute Megakaryocytic Leukemia: A Single Center Study

Introduction Acute megakaryocytic leukemia (AMKL) comprises 4-15% of all acute myeloid leukemia (AML) diagnoses in pediatric patients. Unlike patients with Down syndrome who have a >80% expected survival, the 5-year overall survival (OS) in patients with de novo AMKL ranges between 14-49%. While treatment intensification has improved the outcome of these patients over the last few decades, the role of hematopoietic cell transplantation (HCT) in these patients in complete remission (CR) is often debated. To better define the role of HCT, we evaluated the outcomes of pediatric patients who underwent their first HCT at our institution from October 1990 to January 2021. Methods We conducted a retrospective analysis using patient, disease, and transplant-related data collected during routine clinical care. Kaplan-Meier curves were generated to estimate survival probabilities in pre-specified groups and compared using the log-rank test. Multivariable analysis was performed using Cox proportional hazards models to assess the role of various patient and transplant-related factors on survival. The cumulative incidence of relapse (with death as competing risk) was estimated by the Fine-Gray multivariable models and compared using Gray's test. Results Our study included 53 patients. The median age at HCT was 2.3 (range 0.9-19.7) years. The median time of follow-up was 10.3 (range 0.9-346.6) months. At the time of HCT, 56.6% of patients were in CR1, 5.7% were in CR2 and 37.7% had active/refractory disease. Nine (17%) patients received an HCT from a matched sibling donor, 25 (47.2%) from a matched unrelated donor, and 19 (35.8%) from a haploidentical donor. Twenty-two (41.5%) patients relapsed after HCT at a median duration of 2.8 (range 0.6-10.5) months, and 31 (58.5%) patients died at a median duration of 4.3 (range 0.9-15.9) months. The one-year OS estimates trended higher in patients undergoing transplant in more recent decades (1990-2000: 32%, 2000-2010: 46%, 2010-2020: 67%; P = 0.2). Patients who underwent HCT in CR had a significantly higher 1-year OS (57% versus 30%; P < 0.001) and decreased rate of relapse (24% versus 70%; P < 0.001) compared to those who underwent HCT with active/refractory disease. Similarly, in multivariable analysis, being in CR during HCT was associated with improved OS (Hazard Ratio [HR] 0.17, 95% Confidence Interval [CI] 0.07-0.41) and decreased risk of relapse (HR 0.18, 95% CI 0.07-0.46) after adjusting for other pre-specified variables. Conclusion While the overall outcome of patients who undergo HCT for AMKL has improved in the last few decades, it remains suboptimal. Patients who underwent HCT in CR had superior outcomes. Our data supports the notion that patients with de novo AMKL would benefit from HCT when they first achieve CR while we await novel strategies in treating relapsed or refractory AMKL.