NPM1 is the most frequent mutation in acute myeloid leukemia (AML), occurring in approximately 30% of cases and generally associated with a favorable prognosis when not accompanied by FLT3-ITD or adverse cytogenetics. This prognostic advantage, however, may be offset by additional adverse factors such as older age, elevated leukocyte count, secondary AML, DNMT3A co-mutation, and non-ABD NPM1 variants. Measurable residual disease (MRD) monitoring by NPM1 RT-qPCR after induction has emerged as a key prognostic tool, providing guidance for decisions regarding allogeneic stem cell transplantation (allo-HSCT) in first remission. In Latin America, AML outcomes remain poorer than in high-income countries, largely due to higher treatment-related toxicity, delayed transplant access, and socioeconomic constraints in public health systems. Within this context, no prior studies have specifically addressed NPM1-mutated AML or evaluated how these limitations affect outcomes in low-income countries (LMICs). Our study addresses this gap, representing the first report to include the initial implementation of molecular MRD monitoring in this setting.

To describe clinical characteristics and outcomes of patients with NPM1-mutated AML treated at a public cancer center in Brazil and to identify prognostic factors in a real-world setting.

Retrospective observational cohort of 109 adults diagnosed with NPM1-mutated AML between 2018 and 2024 at the Instituto do Câncer (HCFMUSP). Outcomes included overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM). Prognostic factors were evaluated using univariate and multivariate Cox models. MRD by NPM1 RT-qPCR was performed only in type A cases and implemented from 2022 onward.

Median age was 60 years; 56.9% were female. FLT3 mutations were present in 51.4% of tested patients; 38.5% were FLT3-ITD positive. A total of 88 received chemotherapy; 15 underwent allo-HSCT, all in second remission. Among 32 patients evaluated post-induction, 56.3% were MRD negative; after consolidation, 76.5% were MRD negative. Early mortality occurred in 14.8% overall and 19.3% of those receiving chemotherapy. Five-year OS was 19.9% overall and 24.7% among treated patients. FLT3-ITD was strongly associated with poor survival (5-year OS <5%). OS was ∼50% in patients <50 years and 25% in those ≥50 years. In chemotherapy treated patients, 5-year EFS was 18.9%; CIR was 46.7% and NRM 34.4%. Univariate analysis linked older age, thrombocytopenia, high blast count, elevated C-reactive protein (CRP), hypoalbuminemia, and FLT3 mutation to worse OS. Persistent MRD after induction I also predicted poor outcomes. In multivariate models, FLT3-ITD (HR = 2.51), older age (HR = 1.03), and hypoalbuminemia (HR = 0.58) were independently associated with worse OS. FLT3-ITD and elevated CRP remained significant for EFS.

This study reveals notably poor outcomes in a cohort of NPM1-mutated AML patients treated in the Brazilian public system, particularly among those with FLT3-ITD and older age. High early mortality, limited access to FLT3 inhibitors, and delayed implementation of MRD-guided post-remission strategies likely contributed. These findings reinforce the need to improve access to molecular diagnostics, targeted therapies, and allogeneic transplantation across all treatment phases.