Experience Using Anti-Thymocyte Globulin With Post-Transplantation Cyclophosphamide for Graft-Versus-Host Disease Prophylaxis in Peripheral Blood Haploidentical Stem Cell Transplantation

Abstract

Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P=.006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P=.824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P=.847), RFS (HR 0.984, P=.955), and in NRM (HR 1.38; P=.348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.