Thrombotic and hemorrhagic complications in NPM1-mutated AML: Association with APL-like immunophenotype and impact on...

NPM1-mutated acute myeloid leukemia (AML) is generally classified as favorable risk; however, early mortality remains a concern. A subset of NPM1-mutated AML exhibits a CD34-low/negative and HLA-DR-low/negative immunophenotype resembling acute promyelocytic leukemia (APL), raising the possibility that these patients may also share an increased susceptibility to coagulation abnormalities. While thrombotic and hemorrhagic complications are well recognized in APL, their frequency and prognostic significance in NPM1-mutated AML remain incompletely defined. In this single-center retrospective study, adult patients with newly diagnosed NPM1-mutated AML were included. Immunophenotyping was performed using multiparametric flow cytometry, and an APL-like immunophenotype was defined by low or absent CD34 and HLA-DR expression. Clinically significant thrombotic and hemorrhagic complications were recorded within the first 100 days, and early mortality (30-, 60-, and 100-day) was assessed as the primary survival outcome. A total of 70 patients were included, of whom 24 (34.3%) had an APL-like immunophenotype. Compared with the non-APL-like group, the APL-like group had lower fibrinogen levels (309.5 [211-421] vs. 410 [214-518] mg/dL; p = 0.015) and higher D-dimer levels (5.73 [2.4-9.2] vs. 2.50 [0.9-5.0] mg/L; p = 0.012) at diagnosis. Clinically significant thrombotic or hemorrhagic complications occurred in 12 patients (17.1%) and were more frequent in the APL-like group than in the non-APL-like group (33.3% vs. 8.7%; p = 0.017). In multivariable analysis, the APL-like immunophenotype (OR, 8.79; 95% CI, 1.46-53.05; P=0.018) and a white blood cell count > 35 × 10⁹/L (OR, 10.96 [1.48-80.92] p = 0.019) were independently associated with these complications. Compared with patients without complications, those with thrombotic or hemorrhagic complications had lower 30-day (66.7% vs. 93.0%; P = 0.006), 60-day (57.1% vs. 91.2%; p = 0.002), and 100-day OS (45.7% vs. 87.6%; p < 0.001). Thrombotic or hemorrhagic complications remained independently associated with 100-day mortality in multivariable Cox analysis (HR, 5.79 [1.85-18.06] p = 0.003). In NPM1-mutated AML, the immunophenotypically defined APL-like subset is associated with a procoagulant profile and an increased risk of clinically significant thrombotic and hemorrhagic complications; importantly, these events were independently associated with early mortality.