Prognostic covariates associated with outcomes in patients with NPM1-mutated acute myeloid leukemia.
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BACKGROUND: NPM1 mutacute myeloid leukemia (AML) patients have greater heterogeneity. However, data on the comprehensive integration of clinical and genetic data in NPM1mutAML patients are limited, especially in the FLT3 inhibitor era. METHODS: Data from consecutive AML patients with NPM1mut/FLT3-ITDwt (n = 203) and NPM1mut/FLT3-ITDmut (n = 115) were reviewed. RESULTS: In NPM1mut/FLT3-ITDwt patients, in multivariate analyses male sex, WBC count ≥19 × 109/L, bone marrow blasts ≥ 70%, NPM1 non-A/B/D type mutation, TET2 mutation and measurable residual disease (MRD) positivity after the first cycle of consolidation were significantly-associated with poor relapse-free survival (RFS) and survival. Based on the adverse prognostic covariates, patients were classified into low-risk (score 0-2, n = 113, 64%), intermediate-risk (score 3, n = 43, 25%) and high-risk (score ≥4, n = 20, 11%) subgroups, with significant differences in 3-year probabilities of RFS and survival (all P values < .001). In NPM1mut/FLT3-ITDmut patients who did not undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT) in CR1, single FLT3-ITD mutation, NPM1 non-A/B/D type mutation, TET2 mutation and MRD positivity after the first cycle of consolidation, poor RFS; platelet ≤60 × 109/L and albumin <40 g/L, poor survival. Patients were classified into low-risk (score 0-2) allo-HSCT (n = 9, 11%) or non-allo-HSCT (n = 26, 31%), and high-risk (score ≥ 3) allo-HSCT (n = 8, 10%) or non-allo-HSCT (n = 40, 48%). The first 3 subgroups had comparable outcomes, but were significantly superior to the high-risk non-allo-HSCT subgroup (all P values for trend = .001-.010). CONCLUSIONS: We identified high-risk AML patients with NPM1mut/FLT3-ITDwt or NPM1mut/FLT3-ITDmut who might consider more intensive therapy.