Prognostic impact of clinico-genetic characteristics and donor types in NPM1-mutated AML undergoing allogeneic hematopoietic stem cell transplantation

临床遗传特征和供体类型对接受异基因造血干细胞移植的NPM1突变型急性髓系白血病患者预后的影响

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Abstract

NPM1-mutated acute myeloid leukemia (AML) is a distinct entity with specific biological and clinicopathological features. Prognosis varies depending on the associated mutations and clinical characteristics. This study evaluated the prognostic factors of NPM1-mutated AML in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We enrolled 139 patients with NPM1-mutated AML who underwent allo-HSCT. The median age at allo-HSCT was 47 years with a median follow-up of 1,134 days. The 3-year cumulative incidence of relapse (CIR), leukemia-free survival (LFS), and overall survival (OS) rates were 15.1%, 78.4%, and 78.0%, respectively. FLT3-ITD mutations showed higher CIR (22.6% vs 5.3%, P = 0.006), lower LFS (70.9% vs 88.1%, P = 0.019), and reduced OS (70.8% vs 87.5%, P = 0.036). FLT3-ITD and DTA mutations indicated adverse prognosis, while IDH1/2 mutations showed improved outcomes. Matched sibling donor (MSD) allo-HSCT patients had higher CIR and lower LFS and OS than unrelated donor (URD) or haploidentical-related donor (HRD) recipients. Pre-HSCT MRD status affected the outcomes, with MRD+ and nCR patients showing worse outcomes. Multivariable analysis identified FLT3-ITD, MSD, and pre-MRD status as significant predictors. In conclusion, FLT3-ITD and DTA mutations are associated with an adverse prognosis, whereas HRD or URD transplants may offer better outcomes than MSD allo-HSCT.

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