Prognostic significance of cytogenetic and molecular features in pediatric acute myeloid leukemia: a meta-analysis

Pediatric acute myeloid leukemia (AML) is a clinically and genetically heterogeneous malignancy with variable outcomes. Accurate risk stratification based on cytogenetic and molecular markers is essential for guiding therapy. However, the prognostic impact of several key genomic alterations remains inconsistent across studies. This meta-analysis aims to evaluate the prognostic significance of cytogenetic and molecular abnormalities in pediatric AML and clarify their association with survival outcomes.

A systematic search was conducted across PubMed, EMBASE, Scopus, Web of Science, and CENTRAL up to May 5, 2025. Studies were included if they reported survival outcomes in pediatric patients (≤ 18 years) with de novo AML and evaluated cytogenetic or molecular markers. Data were extracted and synthesized using a random-effects model. Hazard ratios (HRs) or risk ratios (RRs) were pooled for overall survival (OS), event-free survival (EFS), disease-free survival (DFS), complete remission (CR), and relapse risk (RR). Heterogeneity was assessed using I² statistics, and risk of bias was evaluated using the Newcastle-Ottawa Scale.

Thirty-nine studies encompassing over 1,645 pediatric patients were included in the meta-analysis. WT1 overexpression was significantly associated with OS (RR = 1.38, 95% CI: 1.17-1.63). KIT mutations were linked to inferior OS (RR = 0.69, 95% CI: 0.57-0.84), but not to CR, DFS, or relapse risk. FLT3-ITD mutations showed no consistent prognostic effect (RR = 0.97, 95% CI: 0.65-1.46), with substantial heterogeneity (I² = 83%). CEBPA mutations did not significantly impact EFS (RR = 1.00, 95% CI: 0.93-1.07), and neither RAS mutations nor EVI1 overexpression demonstrated prognostic relevance. Publication bias was minimal, and sensitivity analyses confirmed the robustness of pooled estimates.

WT1 overexpression and KIT mutations (in selected cytogenetic contexts) are validated as adverse prognostic indicators in pediatric AML. Conversely, FLT3-ITD and CEBPA mutations require nuanced interpretation due to variable effects and methodological heterogeneity. These findings support the integration of molecular profiling into pediatric AML risk stratification and underscore the need for harmonized, prospective studies to refine prognostic models in this population.