Reduced cytomegalovirus reactivation and viremia without increasing GVHD after URD-PBSCT: A prospective study using targeted ATG dosing strategy.

Background: Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation (allo-HCT) to prevent severe graft-versus-host disease (GVHD) and graft failure. Insufficient ATG exposure may reduce its effectiveness in GVHD prophylaxis, while excessive exposure can elevate the risk of viral reactivation, non-relapse mortality (NRM), and disease relapse. Based on monitoring ATG (Thymoglobulin, Sanofi, Lyon, France) concentrations, we developed an ATG-targeted dosing strategy and conducted a prospective, single-arm study on patients undergoing unrelated donor peripheral blood stem cell transplantation (URD-PBSCT) to evaluate its efficacy and safety. Methods: We enrolled 30 patients with malignant hematological diseases who underwent URD-PBSCT between January 2020 and June 2023. All patients received an ATG-targeted dosing strategy, involving a 4-day administration of ATG: 1.5 mg/kg on day -5, 2.5 mg/kg on day -4, with dose adjustments on day -3 and day -2 to achieve an optimal area under the concentration-time curve (AUC) for active ATG. Engraftment, viral infections, acute and chronic GVHD, relapse, and survival outcomes were statistically analyzed. A historical cohort of 38 patients who underwent URD-PBSCT between December 2014 and December 2020 was used for comparison. Patients in the historical cohort received a fixed total dose of 10 mg/kg ATG from day -5 to day -2. Results: All patients in the targeted dosing cohort achieved successful neutrophil and platelet engraftment with 100% donor chimerism. The cumulative incidence of cytomegalovirus (CMV) reactivation and persistent CMV viremia at 180 days post-transplantation was 30.0% and 16.7%, respectively. The cumulative incidences of Epstein-Barr virus (EBV) reactivation and persistent EBV viremia at 180 days were 46.7% and 23.3%, respectively. The cumulative incidences of grades II-IV and III-IV acute GVHD at 100 days were 49.4% and 9.3%, respectively. The 1-year cumulative incidence of relapse (CIR) was 10.0%, the 1-year NRM was 10.0%, the 1-year disease-free survival (DFS) was 80.0%, and the 1-year overall survival (OS) was 86.7%. Compared with the historical cohort, the targeted dosing cohort showed significantly lower the cumulative incidences of CMV reactivation (30.0% Conclusions: Utilizing a targeted ATG dosing strategy in URD-PBSCT resulted in a lower incidence of CMV reactivation and viremia without increasing the risk of acute or chronic GVHD. Trial registration: www.clinicaltrials.gov, NCT06572462.