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

<i>NPM1</i>-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 <i>NPM1</i>-mutated AML in patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). We enrolled 139 patients with <i>NPM1</i>-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. <i>FLT3-ITD</i> mutations showed higher CIR (22.6% vs 5.3%, <i>P</i> = 0.006), lower LFS (70.9% vs 88.1%, <i>P</i> = 0.019), and reduced OS (70.8% vs 87.5%, <i>P</i> = 0.036). <i>FLT3-ITD</i> and DTA mutations indicated adverse prognosis, while <i>IDH1/2</i> 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 <i>FLT3-ITD</i>, MSD, and pre-MRD status as significant predictors. In conclusion, <i>FLT3-ITD</i> and DTA mutations are associated with an adverse prognosis, whereas HRD or URD transplants may offer better outcomes than MSD allo-HSCT.