Abstract Background Acute lymphoblastic leukemia (ALL) represents the most prevalent pediatric malignancy. The Chinese Children's Cancer Group for ALL (CCCG-ALL) constitutes China's largest collaborative pediatric ALL treatment consortium. From 2015 to 2020, 7,640 pediatric ALL cases were treated under the CCCG-ALL protocol, achieving a 5-year overall survival (OS) of 91% and event-free survival (EFS) of 80%. Current HSCT recommendations are limited to relapsed patients, TCF3::PBX1-positive cases, and select high-risk MLL-rearranged infant leukemias.Objective To evaluate the efficacy and appropriateness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) indications within the CCCG-ALL-2015 protocol and identify key prognostic determinants affecting transplantation outcomes.Methods We retrospectivly analyzed pediatric patients who received allo-HSCT between January 1, 2015, and December 31, 2019 across 20 collaborating hospitals in China. Of 7,640 patients treated under CCCG-ALL-2015, 378 (4.95%) underwent allo-HSCT, with complete transplant data available for 313 patients. Survival analyses employed Kaplan-Meier methodology with Log-rank comparisons. Prognostic variables were evaluated using Cox proportional hazards modeling.Results Among 313 children (209 males, 104 females), B-ALL predominated with 269 cases versus 44 T-ALL cases. Median follow-up duration was 2.02 years (range: 0.02-6.67 years). Five-year OS and EFS were 60.8% and 56.1%, respectively, with cumulative relapse incidence of 26.6% and treatment-related mortality of 14.1%. Among 124 high-risk patients meeting CCCG-ALL-2015 criteria, only 30 underwent HSCT at first complete remission (CR1) according to protocol recommendations, achieving superior 5-year OS compared to chemotherapy-only or transplantation at second or later remissions (≥CR2) cohorts (65.4% vs. 52.2% vs. 45.5%). Notably, 20 patients underwent HSCT at non-remission (NR) or partial remission (PR) status, still with approximately half achieving long-term survival (5-year OS: 47.6%; EFS: 40.0%). Donor distribution comprised haploidentical (n=204, 65%), matched unrelated (n=89, 28%), and matched related donors (n=20, 6%). Survival outcomes remained comparable between haploidentical and non-haploidentical donors (OS: 60.9% vs. 61.9%, P=0.91; EFS: 57.3% vs. 55.5%, P=0.40), with similar acute GVHD incidence (58.21% vs. 53.21%, P=0.41). However, haploidentical HSCT was associated with reduced relapse rates (18.9% vs. 29.5%, P=0.032) but increased chronic GVHD incidence (39.3% vs. 25%, P=0.03), predominantly moderate-to-severe forms (60.76% vs. 30.71%, P=0.013). Grade IV aGVHD significantly compromised 5-year OS (26.9% vs. 64.5%, P0.001), primarily due to infection-related mortality (18/19 cases, 94.7%). Conversely, mild cGVHD correlated with superior outcomes compared to absent, moderate, or severe cGVHD (5-year OS: 77.1% vs. 62.3%, 64.7%, 30.7%, P0.001; EFS: 75.1% vs. 56.4%, 61.1%, 25.3%, P0.001). Multivariable analysis revealed no significant survival impact from gender, immunophenotype, risk stratification, fusion genes, number of remissions prior to HSCT, pre-transplant MRD status, conditioning, GVHD prophylaxis, or donor type (all P0.05). Among 39 Ph-positive patients, all achieved complete remission (CR). HSCT at CR1 showed superior 5-year OS (90%) compared to ≥CR2 HSCT (59.7%) and non-HSCT cohorts with end-of-induction MRD-negative (77.32%) or MRD-positive (59.47%) status, though differences were not statistically significant.Conclusion CCCG-ALL-2015 HSCT indications for pediatric ALL demonstrate clinical validity, with high-risk patients deriving transplantation benefit. Importantly, even patients unable to achieve CR may still benefit from HSCT, as evidenced by 40% long-term survival in NR/PR patients, suggesting expanded therapeutic potential beyond current recommendations. Mild cGVHD confers survival advantage in transplant recipients. Philadelphia chromosome-positive patients with persistent MRD may particularly benefit from HSCT at CR1. Extended follow-up periods and larger patient cohorts are essential to validate these findings and refine transplantation criteria.
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