Optimizing Antithymocyte Globulin Dosing in Haploidentical Hematopoietic Cell Transplantation: Long-Term Follow-Up of a Multicenter, Randomized Controlled Trial

Background: Since randomised 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. Methods: In our prospective, multi-center, randomized trial, 408 patients 14 to 65 years of age with acute leukemia who underwent myeloablative haploidentical hematopoietic cell transplantation (haplo-HCT) were randomly assigned one to one to ATG dosing of 7.5mg/kg (n =203, ATG-7.5) or 10 mg/kg (n = 205, ATG-10) at 4 sites. We analyzed the long-term clinical outcomes including late effects. The original trial was registered at clinicaltrials.gov as NCT01883180. Findings: Extended follow-up (median 1968 days (range, 1300-2710) 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 = .164), non-relapse mortality (HR: 0.814, 95% CI: 0.526–1.261, P = .357), disease-free survival (HR: 1.074, 95% CI: 0.783–1.473, P = .658), and GVHD-free/relapse-free survival (HR: 1.186, 95% CI: 0.904–1.555, P = . 219) between groups (ATG-7.5 vs ATG-10). 5-year rate of late effects did not differ significantly. However, the infection related deaths rate was much more in ATG-10 cohort compared with that of the ATG-7.5 cohort (18.0% vs 11.3%; P = .069). Interpretation: Patients undergoing haplo-HCT benefit from the use of 7.5 mg/kg ATG as opposed to 10 mg/kg ATG, with the balance between GVHD and infection control. 7.5mg/kg ATG should thus be regarded as the standard regimen in the platform. Trial Registration: The original trial was registered at clinicaltrials.gov as NCT01883180. Funding The National Key Research and Development Program of China. Declaration of Interest: None of the authors has any potential financial conflict of interest related to this manuscript. Ethical Approval: The study protocol was approved by the 8 ethics committee of each participating center.