Poor outcomes of NPM1-mutated AML in Brazil despite traditional risks and recent adoption of molecular monitoring Open Access

Acute Myeloid Leukemia, NPM1 mutation, FLT3 ITD, Measurable Residual Disease, Latin America, Overall Survival

Outcomes of NPM1-mutated AML in Brazil are influenced by limited access to novel therapies and low transplant rates.

NPM1 mutation is the most frequent genetic alteration in acute myeloid leukemia (AML), usually associated with favorable prognosis when not accompanied by FLT3-ITD or adverse cytogenetics, but outcomes in low- and middle-income countries (LMICs) remain poorly described. We conducted a retrospective observational study of 109 patients with NPM1-mutated AML diagnosed between 2018 and 2024 at a Brazilian public cancer center, aiming to evaluate clinical, molecular, and treatment characteristics associated with prognosis and to report early experience with measurable residual disease (MRD) monitoring. Clinical, laboratory, and molecular data were collected, and overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) were estimated. Prognostic factors were assessed with Cox regression models. The median age was 60 years and 56.9% were female. FLT3-ITD was present in 38.5%, but only three patients received FLT3 inhibitors. Among treated patients, 67% achieved complete remission and 56.3% reached MRD negativity after induction. Fifteen underwent allo-HSCT, all after second remission. At five years, OS and EFS were 24.7% and 18.9%, respectively. Outcomes were markedly inferior to those reported in high-income countries, likely reflecting limited access to targeted therapies and transplantation in first remission, underscoring disparities in AML care across LMICs.