Allogeneic hematopoietic stem cell transplantation is associated with improved long-term survival and molecular MRD clearance in KMT2A -altered AML

BACKGROUND KMT2A-altered acute myeloid leukemia (AML) is a rare, aggressive high-risk subtype. The prognostic value of flow-cytometric phenotypic MRD versus KMT2A gene-specific molecular MRD, and the role of allogeneic hematopoietic stem cell transplantation (Allo-HSCT), remain poorly defined. METHODS This single-center retrospective cohort enrolled 155 newly diagnosed adolescent and adult patients with KMT2A-altered AML. Treatment response, MRD status, and survival were analyzed by Kaplan-Meier and multivariate Cox regression; time-dependent Cox regression was used as a sensitivity analysis to account for guarantee-time bias. RESULTS Among 153 evaluable patients, the complete remission rate was 70.7% and overall response rate 78.9%, with median RFS of 12.4 months and OS of 16.4 months. After excluding transplanted patients, the three non-transplant regimens yielded similar survival, indicating no inherent advantage of induction regimens. Flow-MRD-negative patients had superior OS, and concurrent KMT2A molecular MRD negativity conferred the best outcomes. Allo-HSCT was associated with a markedly higher rate of sustained molecular MRD negativity (74.6% vs. 14.4%, p < 0.0001). On multivariate analysis, persistent molecular MRD positivity and absence of Allo-HSCT independently predicted inferior RFS and OS; after time-dependent adjustment, Allo-HSCT showed only a non-significant trend, while molecular MRD positivity remained the dominant adverse prognostic factor. CONCLUSION In KMT2A-altered AML, sustained KMT2A molecular MRD negativity is the key determinant of favorable long-term survival. Allo-HSCT promotes molecular MRD clearance and may serve as a consolidation strategy to achieve deep molecular remission.