Monitoring the KMT2A gene post-chemotherapy independently predicts the relapse and survival risk after allogeneic haematopoietic stem cell transplantation.

Abstract

This study evaluated the kinetics of KMT2A-r during chemotherapy and its impact on allogeneic haematopoietic stem cell transplantation (allo-HSCT) outcomes. KMT2A-r was assessed post-induction (MRD1), after the first (MRD2) and second (MRD3) consolidations and pre-transplant (MRD4) in 52 patients with acute myeloid leukaemia (AML). KMT2A-r significantly decreased from diagnosis to MRD2 (p < 0.001 for diagnosis vs. MRD1; p = 0.019 for MRD1 vs. MRD2). The incidence of KMT2A-r negativity (57.5%) peaked at MRD2. KMT2A-r status at each time point significantly affected post-transplant outcomes. Cluster analysis identified four KMT2A-r kinetic profiles: persistently negative (-/-), turned negative at transplant (+/-), turned positive at transplant (-/+) and persistently positive (+/+). The (-/-) group had the best outcomes, with a cumulative incidence of relapse (CIR) of 13.0%, overall survival (OS) of 82.0% and leukaemia-free survival (LFS) of 81.7%. The (+/+) group had the worst prognosis, with a CIR of 58.8%, OS of 29.4% and LFS of 23.5%. KMT2A dynamics were an independent risk factor for CIR (Hazard ratio [HR] = 11.070, 95%CI 2.395-51.165, p = 0.002), LFS (HR = 9.316, 95%CI 2.656-32.668, p < 0.001) and OS (HR = 7.172, 95%CI 1.999-25.730, p = 0.003). In conclusion, KMT2A-r status after chemotherapy and its kinetics are significant HSCT prognostic indicators.