Efficacy and Safety of Matched Unrelated Donor Hematopoietic Stem Cell Transplantation for Non–Down syndrome Acute Megakaryoblastic Leukemia: A Long-Term Follow-Up Study

Non-Down syndrome acute megakaryoblastic leukemia (non-DS-AMKL) is a rare and aggressive subtype of pediatric acute myeloid leukemia (AML) with a heterogeneous genetic landscape and poor prognosis. Matched unrelated donor hematopoietic stem cell transplantation (MUD-HSCT) is a potentially curative approach, yet data on its long-term efficacy and safety remain limited. We retrospective analysis of 12 pediatric non-DS-AMKL patients undergoing first MUD-HSCT (2016–2025) with outcomes—overall survival (OS), leukemia‑free survival (LFS), non‑relapse mortality (NRM), cumulative incidence of relapse (CIR), and transplant-related complications—estimated by Kaplan–Meier and competing-risk models. Among 12 patients (median age: 2 years, range: 1–7), genetic profiling revealed fusion genes in 50% of patients—predominantly KMT2A rearrangements—and complex cytogenetics in 50%. All 5 deceased patients had adverse cytogenetics or fusion alterations. Engraftment was achieved in 100% of patients, with median neutrophil and platelet recovery times of 15 and 10 days, respectively. The median follow-up was 32 months (range, 2.0–105.3), 7/12 (58.3%) patients remained alive with a median follow-up of 53.9 months (range, 28.1–105.3). Day-100 Transplant-Related Mortality (TRM) rate was 16.7%, with 5-year OS and LFS rates of 58.3% (95% CI, 30.4–86.2%) and a CIR as well as NRM of 25% (95% CI, 9.4–66.6%). Additionally, grade 3–4 acute GVHD occurred in 25% and chronic GVHD in 25% of patients, while viral reactivation rates for CMV and EBV were 66.7% and 33.3%, respectively. This represents the first decade-long follow-up study of MUD-HSCT in non-DS-AMKL. MUD-HSCT is feasible for non-DS-AMKL, with rapid engraftment and durable remission in CR patients. Precision risk stratification and post-transplant surveillance strategies are essential to improve outcomes in this population.