Total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL) is efficacious; however, the long-term side-effects are concerning. 

A new study published in the Journal of Clinical Oncology investigated whether preparative combination chemotherapy could replace TBI in such patients.

This was a randomized, controlled, open-label, international, multicenter, phase III, noninferiority study wherein patients ≤ 18 years at diagnosis, 4-21 years at HSCT, in complete remission pre-HSCT—and with an HLA-compatible related or unrelated donor—were randomly assigned to myeloablative conditioning with fractionated 12 Gy TBI and etoposide versus fludarabine, thiotepa, and either busulfan or treosulfan. The noninferiority margin was 8%. A futility stopping rule would halt random assignment if chemoconditioning was significantly inferior to TBI.

During the study period – 2013-18, 543 patients were screened and 417 were randomly assigned. Among these 212 received TBI, and 201 received chemoconditioning. The stopping rule was applied on March 31, 2019; the median follow-up was 2.1 years. In the intention-to-treat population, 2-year overall survival (OS) was significantly higher following TBI versus chemoconditioning. Meanwhile, the two-year cumulative incidence of relapse and treatment-related mortality were 0.12 and 0.02 following TBI and 0.33 and 0.09following chemo-conditioning, respectively.

The results showed reduced OS and lower relapse risk following TBI plus etoposide compared to chemoconditioning. Therefore, TBI plus etoposide was recommended for patients > 4 years of age, with high-risk ALL undergoing allogeneic HSCT.

Source: Journal of Clinical Oncology. 2021 Feb 1;39(4):295-307. doi: 10.1200/JCO.20.02529.