Blinatumomab versus chemotherapy in pediatric B-ALL: A meta-analysis of randomized trials in relapsed and high-risk frontline disease

Background B-cell acute lymphoblastic leukemia (B-ALL) is the most common pediatric cancer, comprising almost 25 % of childhood malignancies. Despite advances in chemotherapy, relapse remains a major cause of treatment failure, particularly in high-risk patients. Blinatumomab, a CD19-directed bispecific T-cell engager, approved for relapsed/refractory and measurable residual disease (MRD)-positive B-ALL, but its benefit in pediatric patients at increased risk of relapse remains uncertain. Objective To evaluate whether adding blinatumomab to chemotherapy improves survival and MRD outcomes in pediatric patients with relapsed/refractory or high-risk frontline B-ALL. Methods We searched PubMed, EMBASE, and Cochrane Library through March 2025, following PRISMA 2020 guidelines. Randomized controlled trials (RCTs) evaluating blinatumomab versus chemotherapy in pediatric B-ALL patients at increased risk of relapse. Primary outcomes were disease-free survival (DFS). Overall survival (OS), MRD, and adverse effects were also assessed. Risk ratios (RRs) with 95 % confidence intervals (CIs) were pooled using random-effects models. Results Four RCTs involving 2,011 patients were included. Blinatumomab significantly improved DFS (RR: 0.63, 95 % CI: 0.47-0.83; P = 0.001) and OS (RR: 0.62, 95 % CI: 0.47-0.84; P = 0.002). No statistically significant improvement was observed in MRD clearance (RR: 1.21, 95 % CI: 0.56-2.62; P = 0.62). Adverse event rates were similar between groups (RR: 1.00, 95 % CI: 0.57–1.75; P = 0.99), although heterogeneity was high. Conclusion This meta-analysis suggests that adding Blinatumomab to chemotherapy improves survival in pediatric relapsed/refractory B-ALL and selected high risk frontline populations. However, limited frontline evidence and variability in MRD and toxicity reporting warrant further standardized pediatric studies. © 2026 The Author(s).