Optimizing antithymocyte globulin dosing in haploidentical hematopoietic cell transplantation: long-term follow-up of a multicenter, randomized controlled trial

Abstract Given that randomized studies testing the long-term impact of antithymocyte globulin (ATG) dosing are scarce, we report the results of an extended follow-up from the original trial. In our prospective, multicenter, randomized trial, 408 leukemia patients 14–65 years of age who underwent haploidentical hematopoietic cell transplantation (haplo-HCT) under our original “Beijing protocol” were randomly assigned one-to-one to ATG doses of 7.5 mg/kg (n = 203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10.0) at four sites. Extended follow-up (median 1968 d (range: 1300–2710 d) indicated comparable 5-year probabilities of moderate-to-severe chronic graft-versus-host disease (GVHD) (hazard ratio (HR): 1.384, 95% confidence interval (CI): 0.876–2.189, P = 0.164), nonrelapse mortality (HR: 0.814, 95% CI: 0.526–1.261, P = 0.357), relapse (HR: 1.521, 95% CI: 0.919–2.518, P = 0.103), disease-free survival (HR: 1.074, 95% CI: 0.783–1.473, P = 0.658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904–1.555, P = 0.219) between groups (ATG-7.5 vs. ATG-10.0). The 5-year rate of late effects did not differ significantly. However, the cytomegalovirus/Epstein-Barr virus-related death rate was much higher in the ATG-10.0 cohort than in the ATG-7.5 cohort (9.8% vs. 1.5%; P = 0.003). In summary, patients undergoing haplo-HCT benefit from 7.5 mg/kg ATG compared to 10.0 mg/kg ATG based on a balance between GVHD and infection control. ATG (7.5 mg/kg) is potentially regarded as the standard regimen in the platform. These results support the optimization of ATG use in the “Beijing Protocol”, especially considering the potential economic advantage in developing countries.