[Analysis of risk factors for early death in NPM1-mutated acute myeloid leukemia patients]

Objective: To investigate the risk factors for early death (ED) in patients with NPM1-mutated acute myeloid leukemia (NPM1(mut) AML) . Methods: A retrospective analysis was conducted on 405 newly diagnosed primary NPM1(mut) AML patients admitted to the First Affiliated Hospital of Soochow University and the First People's Hospital of Yancheng between June 2018 and June 2023. Clinical and laboratory data at diagnosis were analyzed. Univariate and multivariate logistic regression analyses were used to explore the risk factors for early death in these patients. Results: The median age of the 405 NPM1(mut) AML patients was 53 (14-86) years, with 177 males and 228 females. The most common mutations at diagnosis were in DNMT3A (51.8% ), FLT3-ITD (51.3% ), FLT3-TKD (25.1% ), IDH2 (21.5% ), and TET2 (21.0% ). Thirty-five patients (8.6% ) experienced ED, with causes including 14 cases (40.0% ) of severe infection, 11 cases (31.4% ) of cerebral hemorrhage, 4 cases (11.4% ) of cerebral infarction, and 3 cases (8.6% ) of pulmonary hemorrhage. Compared with non-ED patients, ED patients had a significantly higher proportion of the CD34 and HLA-DR double-negative immunophenotype (CD34(-)/HLA-DR(-)) (71.4% vs 30.0%, P<0.001), a higher incidence of coagulopathy (80.0% vs 27.5%, P<0.001), and a higher incidence of TET2 mutations (40.0% vs 19.1%, P=0.004). Multivariate analysis showed that the Charlson comorbidity index (CCI) (OR=10.540, P=0.003), platelet count (OR=10.980, P=0.001), coagulopathy (OR=7.126, P=0.005), CD34(-)/HLA-DR(-) immunophenotype (OR=6.416, P=0.002), and infection (OR=59.080, P<0.001) were independent risk factors for ED in NPM1(mut) AML patients. Conclusion: Severe infection and bleeding were the main risk factors for ED in NPM1(mut) AML patients, and the CD34(-)/HLA-DR(-) immunophenotype should be considered in risk stratification and clinical management of patients with NPM1(mut) AML to guide early intervention.