Single-Dose Daily Fractionation Is Not Inferior to Twice-a-Day Fractionated Total-Body Irradiation Before Allogeneic Stem Cell Transplantation for Acute Leukemia: A Useful Practice Simplification Resulting From the SARASIN Study

Abstract

Total-body irradiation (TBI) is a major constituent of myeloablative conditioning regimens. The standard technique consists of 12Gy in 6 fractions over a period of 3days. The Standard-fractionation compAred to one-daily fRaction total body irrAdiation prior to tranSplant In LEUkemia patieNts (SARASIN) study aimed to compare standard fractionation with once-daily fractionation before transplant in leukemia. We retrospectively compared TBI regimens delivered in 2993 patients from the European Society for Blood and Marrow Transplantation database, who underwent transplantation between 2000 and 2014 for acute lymphoblastic leukemia (ALL, n=1729) or acute myeloid leukemia (AML, n=1264).TBI was delivered as either 12Gy in 6 fractions (group 1, considered the reference group; 1362 ALL and 857 AML patients), 9 to 12Gy in 2 fractions (group 2, 173 ALL and 256 AML patients), or 12Gy in 3 to 4 fractions (group 3, 194 ALL and 151 AML patients). The median follow-up was 60 and 84months in ALL and AML patients, respectively. At 5years, the leukemia-free survival rate, overall survival rate, relapse incidence, and nonrelapse mortality rate were 46.6%, 50.4%, 28.8%, and 24.6%, respectively, in ALL patients and 46.6%, 48.9%, 29.7%, and 23.6%, respectively, in AML patients. In multivariate analyses, the outcomes of groups 2 and 3 were not statistically different from those in group 1. The cumulative incidence of secondary malignancies (SMs) was significantly higher in group 2 (7.2%; P<10-6 for group 2 vs group 1). However, group 2 was not associated with an increase in SMs when we considered non-T-cell-depleted transplant patients. We showed that the 12-Gy fractionated TBI dose delivered either in 2 fractions or in 1 fraction per day over a period of 3 to 4days resulted in nonsignificant differences in disease control and survival. However, 1-day fractionation may be associated with a higher risk of mucositis and hemorrhagic cystitis. The absence of a significant difference in the SM incidence in the non-T-cell-depleted group should be interpreted with caution in the context of a retrospective study design. Our findings are important to consider for radiation therapy department organization. In-depth analyses of other nonlethal toxicities and late effects are required.