Optimal Dose of Rabbit Thymoglobulin in Conditioning Regimens for Unmanipulated, Haploidentical, Hematopoietic Stem Cell Transplantation: Long-Term Outcomes of a Prospective Randomized Trial

BACKGROUND: Antithymocyte globulin (ATG) is an important component of conditioning regimens to prevent severe graft-versus-host disease (GVHD) in patients undergoing unmanipulated, haploidentical stem cell transplantation (haplo-SCT). However, to the authors' knowledge, the optimal dose of ATG is unknown. METHODS: In this prospective, randomized trial, the authors compared the long-term outcomes of 2 ATG doses (rabbit thymoglobulin) used in myeloablative conditioning before unmanipulated haplo-HSCT. Patients were randomly assigned (1: 1) to received 10mg/kg (ATG-10) or 6 mg/kg (ATG-6) of ATG. Analysis of disease-free survival, GVHD-free/recurrence-free survival (GRFS), disease recurrence, nonrecurrence mortality, and chronic GVHD (cGVHD) included the entire population. Late effects were assessed in disease-free patients who had survived for at least 6 months and had received regular follow-up evaluations. RESULTS: A total of 224 patients were recruited. The median follow-up period was 1614 days (range, 281929 days). The rate of infection-related deaths in ATG-10 arm was double that of the ATG-6 arm (14.3% vs 7.1%; P=.084). The 5-year cumulative incidence was comparable between the ATG-6 and ATG-10 groups for disease recurrence (12.8% vs 13.4%; P=.832) and nonrecurrence mortality (11.6% vs 17.0%; P=.263). The 5-year probability of disease-free survival was comparable between the groups (75.6% vs 69.6%; P=.283). The 5-year cumulative incidence of cGVHD was found to be higher with ATG-6 (75.0% vs 56.3% [P=.007] and moderate-to-severe cGVHD: 56.3% vs 30.4% [ P <.0001]) as well as that for late effects (71.2% vs 56.9%; P=.043). The 5-year probability of GRFS was higher in the ATG-10 group (41.0% vs 26.8%; P=.008). In the multivariate analysis, ATG-10 was found to be associated with a lower risk of cGVHD and improved GRFS. CONCLUSIONS: ATG-10 was found to be associated with better GVHD prevention and superior GRFS, but an increase in infection-related deaths. (c) 2017 American Cancer Society.