Integrated Molecular Risk Stratification and Measurable Residual Disease-Guided Consolidation Improve Outcomes in...

Management of pediatric acute megakaryoblastic leukemia (AMKL) without Down syndrome (non-DS-AMKL) remains challenging due to suboptimal induction responses and poor survival. This study assessed the efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) in non-DS-AMKL and evaluated the role of risk-adapted consolidation strategies, including hematopoietic stem cell transplantation (HSCT) during first complete remission (CR1), guided by genetic profiles and measurable residual disease (MRD) dynamics. In this multicenter retrospective study from China, we analyzed 58 non-DS-AMKL patients treated with FLAG-IDA (n = 50) or daunorubicin, cytarabine, etoposide (DAE) (n = 8) induction, followed by risk-adapted consolidation. FLAG-IDA demonstrated CR rates comparable to those with DAE (first-course: 70.0% vs. 87.5%, p = 0.423; cumulative: 82.0% vs. 87.5%, p = 1.000). Compared with other AML subtypes, non-DS-AMKL showed inferior 5-year overall survival (OS) (61.7% vs. 78.2%, p = 0.001) and event-free survival (EFS) (58.5% vs. 68.8%, p = 0.045), attributable to a higher relapse rate (34.8% vs. 19.5%, p = 0.002). High-risk genetics predicted worse outcomes. HSCT in CR1 significantly improved survival for high-risk or poor responders. CR with MRD negativity after second induction predicted superior OS and EFS (p < 0.001). Risk-adapted HSCT and MRD-guided stratification are critical for non-DS-AMKL management.