The complications of irradiation or busulfan for CAYA before hematopoietic stem cell transplantation: a systematic review and meta-analysis.
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INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) represents a curative therapeutic modality for children, adolescents, and young-adult (CAYA) patients with various life-threatening hematological malignancies and non- malignant haematological disorders. Conditioning regimens, a cornerstone of HSCT, typically involve total body irradiation (TBI) or busulfan (Bu)-based myeloablation. However, the optimal conditioning strategy for CAYA populations remains controversial, and high-quality evidence regarding long-term complications is lacking. This systematic review and meta-analysis aimed to comprehensively compare the efficacy and safety profiles of TBI and Bu-based conditioning regimens in CAYA-HSCT recipients. METHODS: We systematically searched PubMed, Embase, Cochrane Library, Web of Science, Scopus, ClinicalTrials.gov, Wanfang Data, and CNKI databases from inception to August 3, 2025. Eligible studies included prospective or retrospective cohort studies and randomized controlled trials involving CAYA patients (0-25 years) undergoing HSCT with TBI or Bu-based conditioning. Primary outcomes were overall survival (OS), event-free survival (EFS), transplant-related mortality (TRM), and relapse rate. Secondary outcomes included seven key long-term complications: growth retardation, thyroid dysfunction, hypogonadism, secondary tumors, cataracts, neurological complications, and chronic graft-vs.-host disease (cGVHD). RESULTS: A total of 4,928 studies were identified, with 26 ultimately included in the meta-analysis. The results showed that Bu conferred survival benefits for patients with AML and cohorts comprising both malignant and non-malignant disease cases, whereas TBI yielded superior EFS and relapse-control outcomes in ALL patients. Five long-term complications (growth retardation, thyroid dysfunction, hypogonadism, secondary tumors and cataracts) occurred at significantly lower rates in the Bu group. Sex-related heterogeneity was observed for hypogonadism with higher Bu-associated risk in one female- only cohort. No significant differences were observed in neurological complications or cGVHD between the two groups. DISCUSSION: In conclusion, conditioning-regimen selection should be individualized according to disease subtype. For ALL patients, clinicians need to balance the survival- and relapse-preventive advantages of TBI against its long-term toxic effects on children's growth, development and vital organs. For AML patients, the survival benefits of Bu-based conditioning should be weighed against sex- dependent toxic risks. Early preventive-interventional measures and adequate education for patients and guardians are essential for CAYA patients receiving TBI or Bu-based conditioning.