Reduced-dose PTCy Plus Postengraftment Low-dose ATG for GVHD Prophylaxis in Haploidentical PBSC Transplantation.

Post-transplant cyclophosphamide (PTCy) combined with antithymocyte globulin (ATG) is increasingly used for graft-versus-host disease (GVHD) prophylaxis after haploidentical hematopoietic cell transplantation (haplo-HCT). However, the optimal timing and dose of this combination remain unclear, particularly with respect to balancing GVHD prevention against treatment-related toxicity and life-threatening infections. In this real-world multicenter cohort study, we evaluated a modified prophylactic strategy incorporating reduced-dose PTCy and delayed low-dose ATG. We retrospectively analyzed 99 patients with hematologic malignancies who underwent first haploidentical HCT at 2 centers. All patients received myeloablative conditioning. Patients received either reduced-dose PTCy, 80 mg/kg total on days +3 and +4, plus a single delayed low-dose ATG, 2.5 mg/kg, administered after neutrophil engraftment (PTCy-ATG group; n = 30), or conventional ATG-based prophylaxis based on the Beijing protocol, consisting of pretransplant ATG, cyclosporine, mycophenolate mofetil, and short-course methotrexate (ATG group; n = 69). The primary endpoint was the cumulative incidence of grade II to IV acute GVHD. The cumulative incidence of grade II to IV acute GVHD was lower in the PTCy-ATG group than in the ATG group (13.8% versus 36.7%; P = .030). The modified regimen was associated with lower incidences of selected transplant-related toxicities. Hemorrhagic cystitis and bloodstream infection both occurred less frequently in the PTCy-ATG group (6.7% versus 34.8%, P = .003; and 3.3% versus 23.2%, P = .019). Grade III-IV acute GVHD, chronic GVHD, nonrelapse mortality, relapse, overall survival, and relapse-free survival did not show significant between-group differences. In multivariable analysis, GVHD prophylaxis regimen was not independently associated with GRFS. Reduced-dose PTCy combined with delayed low-dose ATG was associated with lower rates of grade II to IV acute GVHD and selected transplant-related toxicities, with no clear adverse signal in relapse or survival outcomes. These findings warrant prospective evaluation using contemporary comparator regimens.