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

作者：Ruixin Li, Jiaxin Cao, Mingyang Wang, Jinting Fan, Yang Yang, Hongye Gao, Fengjiao Wang, Donglin Yang, Rongli Zhang, Weihua Zhai, Yigeng Cao, Jialin Wei, Aiming Pang, Yi He, Sizhou Feng, Mingzhe Han, Erlie Jiang · 发表于：Blood Science · 年份：2025 · DOI：10.1097/bs9.0000000000000267 · 被引用次数：1 · 研究领域：Acute Myeloid Leukemia Research、Hematopoietic Stem Cell Transplantation、Nuclear Structure and Function

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...