Vascular complications in NPM1-Mutated acute myeloid leukemia: clinical features and prognosis

Although nucleophosmin 1 (NPM1) mutation is generally considered a favorable prognostic biomarker in acute myeloid leukemia (AML), its clinical behavior is heterogeneous. A subset of NPM1-mutated patients continues to experience adverse outcomes despite their favorable genotype. We conducted a retrospective analysis of newly diagnosed NPM1-mutated AML patients treated at The First Affiliated Hospital of China Medical University, between June 2015 and June 2025, aiming to identify clinical characteristics and prognostic determinants associated with vascular events. A total of 120 patients fulfilled the inclusion criteria, with a median age of 55 years. The median follow-up was 20.7 months, and the median event-free survival (EFS) was 16.2 months. Forty-seven patients(39.2%) developed major organ vascular events. Compared to those without vascular events, patients who experienced vascular complications more frequently exhibited a CD34⁻/HLA-DR⁻ immunophenotype and harbored concomitant FLT3-ITD/TKD mutations. Notably, of the 37 classified as favorable-risk AML, 10(27%) suffered vascular events. One-year estimated overall survival (OS) was significantly lower in the vascular event group than in the non-event group (48.6% vs. 75.8%, p = 0.008), while the 60-day mortality rate was markedly higher (27.3% vs. 3.0%, p < 0.001). Both a CD34⁻/HLA-DR⁻ immunophenotype and FLT3-ITD/TKD co-mutation were identified as risk factors for vascular events. In summary, patients with NPM1-mutated AML who developed vascular events predominantly exhibited an “APL-like” (acute promyelocytic leukemia-like) phenotype, and FLT3-ITD/TKD co-mutation emerged as an independent predictor of vascular complications in this subgroup.