Temporal Improvement in Post‐Relapse Survival Among Children With Relapsed B‐Cell Acute Lymphoblastic Leukemia in China: A Multicenter Retrospective Cohort Study, 2015–2023

ABSTRACT Objective Whether post‐relapse survival in pediatric B‐cell acute lymphoblastic leukemia (B‐ALL) has improved in contemporary Chinese practice remains unclear. We evaluated temporal changes in survival and salvage treatment patterns among children with relapsed B‐ALL treated during 2015–2023. Methods This multicenter retrospective cohort study included children and adolescents with relapsed B‐ALL, grouped by year of first relapse into Stage I (2015–2017), Stage II (2018–2020), and Stage III (2021–2023). The primary endpoint was overall survival (OS) from first relapse. Sensitivity analysis used a composite endpoint of death or treatment abandonment. Kaplan–Meier analysis, multivariable Cox regression, and inverse probability of treatment weighting (IPTW) were applied. Results Among 585 reviewed records, 527 patients had B‐ALL with available first‐relapse dates, and 504 comprised the primary survival cohort: 72 in Stage I, 309 in Stage II, and 123 in Stage III. Relapse characteristics and treatment patterns changed across eras, with increasing use of chimeric antigen receptor T‐cell therapy and targeted therapies in later periods. The 24‐month OS rates were 52.1% (95% CI, 41.3%–65.6%), 66.5% (95% CI, 61.1%–72.4%), and 82.9% (95% CI, 75.3%–91.2%) for Stages I, II, and III, respectively (log‐rank p < 0.001). In multivariable analysis, Stage III was associated with lower mortality than Stage I (HR, 0.421; 95% CI, 0.222–0.797; p = 0.008), whereas Stage II was not significantly associated with reduced mortality (HR, 0.825; 95% CI, 0.540–1.262; p = 0.375). Early or very early relapse, bone marrow relapse, combined relapse, and other or unknown relapse sites were associated with worse outcomes. Findings were consistent in sensitivity and IPTW‐weighted analyses. Conclusion Post‐relapse survival in pediatric B‐ALL improved substantially across treatment eras, with the clearest benefit in Stage III. This improvement coincided with increasing use of chimeric antigen receptor T‐cell and targeted therapies. Early relapse and marrow‐involving relapse remained major adverse prognostic factors.