FLT3-ITD with NPM1 and/or DNMT3A co-mutations in acute myeloid leukemia: prognostic significance and the role of maintenance therapy post-transplantation

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FLT3-ITD , NPM1 , and DNMT3A mutations are common in acute myeloid leukemia (AML). However, the prognostic role of FLT3-ITD combined with NPM1 and/or DNMT3A mutations after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. In this retrospective study, 100 AML patients were selected from a cohort of 1292 who underwent allo-HSCT between 2014 and 2024. Patients were stratified by co-mutation profiles to compare prognosis, identify predictors of survival and relapse, and assess the efficacy of maintenance therapy. With a median follow-up after allo-HSCT of 16.1 months (interquartile range 8.1–26.2), 2-year overall survival (OS) rates were 65.1%, 68.3%, and 67.1%; leukemia-free survival (LFS) rates were 61.6%, 68.7%, and 63.2%; and cumulative incidence of relapse (CIR) rates were 16.9%, 12.5%, and 15.8%, respectively. No significant differences were observed among the groups. In multivariate analysis with FLT3 inhibitor as a time-dependent covariate, FLT3-ITD measurable residual disease (MRD) positivity prior to allo-HSCT was independently associated with inferior OS (hazard ratio [HR] = 3.51, 95% CI 1.34–9.17), LFS (HR = 3.05, 95% CI 1.26–7.35), and CIR (HR = 4.78, 95% CI 1.55–14.81). In contrast, posttransplant maintenance therapy with FLT3 inhibitors independently conferred a favorable impact on OS (HR = 0.15, 95% CI 0.03–0.66), LFS (HR = 0.24, 95% CI 0.07–0.83), CIR (HR = 0.10, 95% CI 0.01–0.66), and nonrelapse mortality (NRM) (HR = 0.25, 95% CI 0.07–0.89). In conclusion, FLT3-ITD -based double or triple mutations showed comparable posttransplant outcomes. FLT3-ITD MRD status and early maintenance therapy were key prognostic and therapeutic factors.

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