Real-world outcomes of children with first relapsed acute lymphoblastic leukemia treated according to the ALL-IC REL 2016 guideline in Türkiye

Relapsed acute lymphoblastic leukemia (ALL) remains a major challenge in pediatric oncology, particularly where access to modern immunotherapies is limited. This national multicenter study evaluated real-world outcomes of children with first relapsed ALL treated according to the ALL-IC REL 2016 guideline in Türkiye. Children aged < 21 years with first ALL relapse between February 2017 and June 2022 and registered in the REDCap database were included. Overall survival (OS), event-free survival (EFS), remission rates, induction failure, second relapse, treatment-related mortality, and prognostic factors were analyzed. A total of 132 patients from 27 centers were evaluated; 67 were standard-risk and 65 high-risk. After induction, second complete remission was achieved in 81.8%, while induction failure occurred in 17.4%. During follow-up, 37.1% developed a second relapse and 64 patients died. The estimated 5-year OS and EFS rates were 51.4% and 43.2%, respectively. Outcomes were significantly better in standard-risk than in high-risk patients (5-year OS: 65.4% vs. 37.5%; 5-year EFS: 57.3% vs. 29.0%; p < 0.001 for both). Very early relapse and age ≥ 10 years at relapse were associated with inferior outcomes, while end-of-induction flow cytometric MRD ≥ 0.1% showed an adverse trend for both OS and EFS. Deaths in remission and treatment-related mortality remained substantial. The ALL-IC REL 2016 guideline was feasible in Türkiye and yielded encouraging outcomes in standard-risk patients. However, high-risk survival remained suboptimal, highlighting the need for standardized MRD assessment, improved supportive care, refined transplant strategies, and broader immunotherapy access.