Body of evidence.
Top Line: Is total body irradiation (TBI) a necessary part of conditioning for stem cell transplant (HSCT) in children with high-risk acute lymphoblastic leukemia (ALL)?
The Study: TBI is a standard part of many conditioning regimens for HSCT in ALL. However, long-term effects of radiation in children have led some to omit TBI in favor of myeloablative chemo conditioning regimens. The FORUM trial was designed to see if overall survival with a chemo-only myeloablative conditioning regimen is non-inferior to TBI-based conditioning in children (4 years or older) with high-risk ALL. In the TBI arm, patients received 12 Gy in 6 fractions over 3 days along with etoposide. In the non-TBI arm, patients received fludarabine, thiotepa, and busulfan or treosulfan. The trial was stopped early after over 400 of a planned 1000 patients were enrolled because overall survival at 2 years was significantly higher with TBI (91%) compared to non-TBI (75%). Event-free survival at 2 years was also superior with TBI (86%) than without (58%). Both outcomes remained significantly higher in subsets of patients in first complete remission (CR) and second CR after relapse. Treatment-related mortality was also significantly higher in the non-TBI arm with more than twice as many patients dying without relapse in the non-TBI arms (3.6% vs 7.3% busulfan, 10% treosulfan).
TBL: In children with high-risk ALL receiving HSCT, omission of TBI from the conditioning regimen results in inferior overall survival and increased treatment-related mortality. | Peters, J Clin Oncol 2020