Genomic Landscape and Clinical Outcomes of Advanced Pediatric Myelodysplastic Syndromes

Pediatric myelodysplastic syndromes (MDS) differ from adult MDS, and their genetic basis is poorly understood. This study characterizes the genomic features and clinical outcomes of advanced pediatric MDS.

In this retrospective study, next-generation sequencing was performed on 63 pediatric patients with advanced MDS, including 46 with MDS with excess blasts (MDS-EB) and 17 with MDS-EB in transformation (MDS-EB-T, 2016 WHO classification), to detect somatic and potential germline variants.

Mutations in 53 genes were detected in 49 patients (77.8%), with a median of 2 variants per patient (range, 0-8). Alterations in the RAS/MAPK pathway were most common, occurring in 28 patients (44.4%). Monosomy 7 significantly co-occurred with SETBP1, ETV6, and GATA2 mutations (p < 0.01). Time-dependent analyses showed HSCT improved 2-year overall survival (OS, 42.6% vs. 84.5%, p = 0.003) and event-free survival (EFS, 37.3% vs. 58.2%, p = 0.011). In multivariate analyses, HSCT was strongly associated with improved OS and EFS (p < 0.01). PTPN11 mutation remained an independent predictor of poorer OS and EFS (p < 0.05), and MDS-EB-T subtype independently predicted inferior EFS (p < 0.05).

In advanced pediatric MDS, HSCT was associated with improved survival, whereas PTPN11 mutations emerged as an adverse prognostic factor.