Targeted dosing of anti-thymocyte globulin in adult unmanipulated haploidentical peripheral blood stem cell transplantation: A single-arm, phase 2 trial.

Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. To investigate the optimal dosing of ATG, we established a targeted dosing strategy based on ATG concentration monitoring for haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). The aim of this phase 2 trial is to evaluate the safety and efficacy of the ATG-targeted dosing strategy in adult unmanipulated haplo-PBSCT. ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on -3 days and -2 days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days. Between December 2020 and January 2022, 66 haplo-PBSCT patients were enrolled and 63 of them were evaluable with a median follow-up of 632 days. The cumulative incidence of CMV reactivation was 36.7% and that of EBV was 58.7%. The 1-year disease-free survival was 82.5%, overall survival was 92.1%, and CD4+ T-cell reconstruction on +100 days was 76.8%. The most common severe regimen-associated toxicities (> grade 3) were infections (51.5%) and gastrointestinal toxicity (25.5%). A total of 102 haplo-PBSCT patients who received the conventional fixed ATG dose (cumulative 10 mg/kg) comprised historical control. The outcomes in historical control were inferior to those of phase 2 trial cohort (CMV reactivation: 70.8%, p < .001; EBV reactivation: 76.0%, p = .024; CD4 + T-cell reconstruction: 54.1%, p = .040). In conclusion, ATG-targeted dosing strategy reduced CMV/EBV reactivation and improved survival without increasing GVHD after haplo-PBSCT. These advantages may be associated with accelerated immune reconstitution.