Real-World Outcomes in -ITD Mutated Acute Myeloid Leukemia: Impact of NPM1 Mutations and Allogeneic Transplantation in a Retrospective Unicentric Cohort.

: Acute myeloid leukemia (AML) with internal tandem duplication (-ITD) mutations carries a poor prognosis. While inhibitors like midostaurin show benefits in combination with chemotherapy, the role of allelic ratio (AR), mutation status, and hematopoietic stem cell transplantation (HSCT) remains uncertain. Real-world data can help refine prognostic classification and treatment strategies. : We retrospectively analyzed 37 fit patients with -ITD AML treated with standard "7+3" chemotherapy, with and without midostaurin, between 2013 and 2022. Patients were stratified by -ITD AR, status, and treatment approach. Outcomes assessed included complete remission (CR), disease-free survival (DFS), and overall survival (OS). : Overall, 67.6% achieved CR/CRi. Response rates did not differ significantly by AR (low vs. high: 66.7% vs. 69.2%) or midostaurin use (72.6% vs. 60%; = 0.49). mutations were associated with improved DFS (10.3 vs. 3 months, = 0.036) but not OS. HSCT, performed in 54.1% of patients, mainly in first remission (CR1), significantly prolonged DFS (not reached vs. 5.3 months, = 0.005) and remained an independent predictor in multivariate analysis (HR: 0.160, = 0.039). OS (median 15.1 months) did not vary significantly across subgroups. Among patients achieving CR1, OS was significantly longer in those who underwent HSCT after midostaurin-based induction compared to those not transplanted (median OS not reached vs. 12.8 months; 95% CI, 6.9-18.7; = 0.045), whereas no significant benefit was observed after standard induction. In a landmark analysis restricted to patients transplanted in CR1, those who had received midostaurin-based induction showed a trend toward improved OS compared to those treated with standard induction (median OS not reached vs. 11.5 months; 95% CI, 0.5-25.0; = 0.086). : This real-life study supports the importance of mutations and HSCT in CR1, especially in the midostaurin era, for improving DFS in -ITD AML. These findings support updated guidelines for reducing the prognostic weight of AR and highlight the need for improved post-remission strategies in this setting.