Compared with chemotherapy conditioning, total body irradiation (TBI) may lead to better outcomes prior to allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients with acute lymphoblastic leukemia (ALL), according to research in the Journal of Clinical Oncology.

Patients with ALL commonly receive TBI and etoposide before undergoing HSCT; however there are long-term side effects associated with TBI-based conditioning. A team of investigators aimed to determine whether conditioning with chemotherapy (chemoconditioning) could replace TBI in pediatric patients with high-risk ALL.

The prospective, randomized, controlled phase 3 trial ( Identifier: NCT01949129) enrolled patients with high-risk ALL who were aged 18 years or younger at diagnosis with an indication for HSCT, and were in complete morphological remission before transplantation. The trial was conducted in multiple centers across 20 countries.

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A total of 413 patients were randomly assigned to TBI plus etoposide (n=212) or to chemoconditioning (n=201), which included intravenous fludarabine, thiotepa, and either treosulfan or busulfan. At a median follow-up of 2.1 years, patients receiving TBI had significantly longer overall survival compared with patients receiving chemoconditioning, with 2-year probability of overall survival of 0.91 vs 0.75, respectively (P <.0001). The 2-year event-free survival was also significantly greater among patients treated with TBI compared with chemoconditioning (P <.0001).

Patients who received TBI had lower risk of relapse and treatment-related mortality compared with patients who received chemoconditioning. Because of these findings, the investigators ended randomization early.

Both conditioning regimens carry substantial toxicities. No expected serious adverse events occurred during the trial. At day 100 the most common grade 3 to 4 adverse events in both arms were cytopenia, mucositis, nausea, and infection. Treatment-related mortality occurred in 7 of 194 patients receiving TBI, and in 16 of 186 patients receiving chemoconditioning.

The authors conclude that myeloablative TBI plus etoposide is recommended for high-risk ALL patients older than age 4 years before undergoing HSCT. Patients ineligible for TBI may undergo chemoconditioning, but the relapse rate remains high.

Disclosure: 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 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. Published online December 17, 2020. doi:10.1200/JCO.20.02529

This article originally appeared on Hematology Advisor