Addition of low-dose antithymocyte globulin to post-transplant cyclophosphamide for effective graft-versus-host disease prophylaxis in peripheral blood stem cell transplantation.

BACKGROUND: Post-transplant cyclophosphamide (PTCy) is central to graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic cell transplantation (allo-HCT); however, there remains an opportunity for further advancement. OBJECTIVE: This study aimed to evaluate the efficacy of dual T-cell depletion using low-dose PTCy and antithymocyte globulin (ATG) for GVHD prophylaxis in peripheral blood allo-HCT. METHODS: Patients with acute leukemia or myelodysplastic syndrome (MDS) who received either PTCy or ATG/PTCy for GVHD prophylaxis were included. Transplant outcomes were compared between the PTCy and ATG/PTCy groups. In the ATG/PTCy group, rabbit ATG (3.0-4.0 mg/kg according to recipient absolute lymphocyte count) and dose-attenuated PTCy (50 mg/kg on day +3 and 30 mg/kg on day +4) were administered. RESULTS: A total of 97 patients were included. Neutrophil engraftment was faster in the ATG/PTCy group. There were no significant differences between the two groups in overall survival, relapse-free survival, or GVHD-free, relapse-free survival. The cumulative incidences of relapse, non-relapse mortality, and grade III-IV acute GVHD were comparable between the two groups. In contrast, the ATG/PTCy group showed a lower incidence of moderate-severe chronic GVHD (2-year: 3.7% [95% CI, 0.7%-11.4%] vs. 17.0% [95% CI, 7.3%-30.2%], P = 0.046). On multivariate analysis, ATG/PTCy was independently associated with a lower risk of moderate-severe cGVHD, but not with relapse, non-relapse mortality, or survival outcomes. CONCLUSION: The addition of low-dose ATG to PTCy may further reduce moderate-severe chronic GVHD compared with PTCy alone, without increasing the risk of relapse or NRM, resulting in improved GRFS.