Pediatric patients with acute lymphoblastic leukemia (ALL) may have better overall survival and lower relapse risk when they receive total body irradiation (TBI) before allogeneic hematopoietic stem cell transplantation (HSCT), according to research in the Journal of Clinical Oncology.
TBI is used as a myeloablative conditioning regimen before HSCT for pediatric patients with ALL, but it carries lifelong adverse effects. The study authors sought to determine whether a combination chemotherapy regimen could replace TBI before HSCT in pediatric patients with ALL.
A total of 417 patients were randomly assigned in the FORUM trial, a randomized, controlled, open-label, phase 3, noninferiority study. Patients who were 18 years or younger at diagnosis, in complete remission before HSCT, and who had an HLA-compatible or unrelated donor were included in the study.
Patients were assigned to either TBI plus etoposide or fludarabine, thiotepa, and either busulfan or treosulfan. A total of 212 patients received TBI, and 201 received chemoconditioning. The trial was stopped with a median follow-up of 2.1 years after TBI showed a significantly improved overall survival (OS) than chemoconditioning.
The 2-year probability of OS was 0.91 for patients treated with TBI versus 0.75 for patients treated with chemoconditioning (P <.0001). The 2-year probability of event-free survival (EFS) was 0.86 for TBI versus 0.58 for chemoconditioning (P <.0001).
The 2-year treatment related mortality (TRM) was 0.02 for TBI compared to 0.09 with chemoconditioning (P =.0269). Relapse was the most frequent reason for treatment failure. In the FORUM trial, the relapse incidence was high with chemoconditioning. Patients who relapsed after transplant in the study had a low possibility of cure. The researchers concluded these patients would not benefit from a second HSCT with TBI.
“The composite end point of 2-year GVHD-free, relapse-free survival of 72% (95% CI, 65%-78%) following TBI plus etoposide and 51% (95% CI, 43% to 58%; P =.0003) following chemoconditioning might be a benchmark for future investigations, accounting for second malignancy risk,” the study authors wrote.
Based on these results, the authors concluded that TBI plus etoposide conditioning is recommended for children over age 4.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of authors’ disclosures.
Peters C, Dalle JH, Locatelli F, et al. Total body irradiation or chemotherapy conditioning in childhood ALL: a multinational, randomized, noninferiority phase III study. J Clin Oncol. 2021;39(4):295-307. doi:10.1200/JCO.20.02529