Impact of Graft Source on Outcomes of Pediatric B Cell Acute Lymphoblastic Leukemia: A Secondary CIBMTR Analysis With Pretransplant Measurable Residual Disease Data.

Allogeneic hematopoietic cell transplantation (HCT) is a well-established therapy for high-risk pediatric B cell acute lymphoblastic leukemia (B-ALL). The recent FORUM study in Europe demonstrated decreased rates of relapse and superior overall survival with total body irradiation (TBI) combined with etoposide compared to a non-TBI-based regimen. However, a knowledge gap remains regarding the efficacy of the variety of conditioning regimens utilized globally, and the outcomes that may differ by varying disease status as evaluated by measurable residual disease (MRD) prior to HCT. Moreover, while TBI is commonly considered most effective, the very young disproportionally experience substantial late effects, and a modern analysis of its utility in younger patients is lacking. This study utilized data from the Center for International Blood and Marrow Transplant Research to analyze outcomes in pediatric B-ALL patients (≤18 years old) who underwent first allogeneic HCT with myeloablative conditioning between 2008 and 2017 in the United States. Patients were analyzed based on conditioning regimen used and graft source received. Outcomes included 3-year disease free survival, relapse rate, nonrelapse mortality, and overall survival. Analyses were stratified by age (<3 years versus ≥3 years) and further stratified by the pre-HCT MRD status. Only TBI-based regimens were analyzed in patients aged ≥3 years due to its predominant use in this age group (96.6%). Across the 1045 pediatric patients transplanted for B-ALL, TBI-based regimens were predominantly used over chemotherapy-based regimens. Among patients ≥3 years, 951 (96.6%) received a TBI-based regimen, the majority received as a combination regimen with cyclophosphamide (CY) (38.9%), CY with fludarabine (26.1%), or CY with other agents (25.2%), while a small proportion (9.8%) were treated with non-CY combinations. No significant differences in outcomes were observed among the various TBI-based regimens or donor type in patients ≥3 years when stratified by the MRD status. In the 94 patients aged <3 years, 61 received a TBI containing regimen while 33 received a busulfan-based regimen, demonstrating no trend of relapse reduction by TBI regimens (P = .77). However, the busulfan-based and TBI-based groups varied significantly by median age and thus may represent different ALL subtypes and unaccounted underlying relapse risks. TBI-based conditioning regimens continue to be used predominantly in pediatric B-ALL patients in US centers, complementing European findings and the FORUM trial. Among patients aged ≥3 receiving TBI, CY-based combination regimens were most commonly used. Neither conditioning regimen nor donor type affected main HCT outcomes regardless of the residual disease status. In patients younger than 3 years, busulfan-based regimens had a larger presence and appeared comparably effective to TBI-based regimens. This large-scale analysis highlights the ongoing dependence on highly toxic therapies for B-ALL and the need for further research into alternative strategies that optimize outcomes and lessen the well-described late effects of TBI.