Outcomes of Myeloid Leukemia Associated With Down Syndrome Treated With a Reduced‐Intensity Protocol: A Multicenter Experience in Argentina

BACKGROUND: Children with Down syndrome (DS) have a markedly increased risk of myeloid leukemia (ML-DS). While survival rates approach 90% in high-income settings, treatment-related toxicity remains a critical challenge in other regions. This study evaluated overall survival (OS), event-free survival (EFS), cumulative incidence of relapse (CIR), and treatment-related mortality (TRM) in pediatric patients with ML-DS in Argentina. DESIGN/METHODS: We conducted a multicenter retrospective study of 49 patients with ML-DS (≤18 years) treated between 2008 and 2025. All patients were treated with the GATLA 8-LMAP-2007 protocol, a reduced-intensity regimen based on AML-BFM 98 (four chemotherapy cycles with reduced anthracyclines, omission of high-dose cytarabine and mitoxantrone, eight intrathecal doses, and 1-year maintenance). We did not use cranial irradiation and hematopoietic stem cell transplantation. Survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: We enrolled 49 patients with ML-DS in this study. Most patients were ≤2 years old (59.2%) and presented with the FAB M7 subtype (75.5%). At 48 months, the CIR was 6.9% (standard error [SE] 3.9), and TRM was 12.5% (SE 4.8). Both 48-month EFS and OS were 80.3% (SE 5.9). CONCLUSIONS: In this Argentine cohort, ML-DS treated with an adapted reduced-intensity protocol achieved favorable survival outcomes. However, the TRM of 12.5% highlights the ongoing need to optimize supportive care and further refine strategies to reduce treatment-related toxicity in this population.