Treatment Outcomes and Prognostic Factors in Children with Myeloid Leukemia Associated with Down Syndrome: A Nationwide Polish Retrospective Study.

Background: Significant progress has been achieved in the treatment of children with myeloid leukemia associated with Down syndrome (ML-DS). We aimed to evaluate treatment outcomes and prognostic factors in children with ML-DS treated in Poland. Methods: Thirty-six children with ML-DS treated at pediatric hematology and oncology centers in Poland according to the ML-DS 2006 protocol based on the AML-BFM backbone between 2015 and 2024 were retrospectively analyzed. Results: The estimated 5-year event-free survival (EFS) and overall survival (OS) were 84.3% (95%CI: 72.5-98.1%) and 87.9% (77.4-99.8%), respectively. Although children with a complex karyotype showed numerically lower survival estimates than those with isolated constitutional trisomy 21 or additional cytogenetic abnormalities (OS: 60% [95%CI: 29.3-100%] vs. 90% [73.2-100%] vs. 92.3% [78.9-100%], p = 0.24; EFS: 60% [95%CI: 29.3-100%) vs. 75% [49.6-100%] vs. 92.3% [78.9-100%], p = 0.26), p = 0.26), these differences were not statistically significant. MRD positivity (≥0.1%) after the second induction cycle was identified as an adverse prognostic factor in the univariable analysis (HR = 31.1, 95%CI: 2.74-353.2; p = 0.006). Conclusions: Persistent MRD positivity after the second induction cycle may identify children with ML-DS at increased risk of treatment failure. Larger multicenter studies are needed to validate the prognostic significance of MRD and recurrent molecular alterations to optimize risk-adapted treatment strategies.