Reduced-Dose Post-Transplant Cyclophosphamide (PTCy 40-40) in Allogeneic Hematopoietic Cell Transplantation

Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis after allogeneic hematopoietic cell transplantation has been associated with clinically significant graft and organ toxicity at the standard dose (50 mg/kg/d on days +3, +4). We conducted a 2-center retrospective cohort analysis to assess outcomes after a uniform dose reduction to 40 mg/kg/d on days +3, +4 (PTCy 40-40). The primary objectives were to evaluate cumulative incidence of acute (aGVHD) and chronic GVHD (cGVHD) and relapse. Secondary objectives included assessment of organ toxicity, engraftment, nonrelapse mortality (NRM), progression-free survival (PFS), and overall survival (OS). Patients receiving PTCy 40-40 from November 2020 to March 2025 at 2 academic centers were included. Exclusion criteria were history of aplasia after chimeric antigen receptor T-cell therapy as indication for HCT or history of prior HCT complicated by GF. Only the initial HCT was included for patients who had >1 allogeneic HCT with PTCy. Patients received cyclophosphamide at a dose of 40 mg/kg/day on days +3, +4 after peripheral blood allogeneic HCT. 115 patients received PTCy 40-40. Most patients received reduced-intensity conditioning (80%) from matched unrelated donors (63%). Median follow-up was 9.0 months (range, 4.9-28.8). Median time to neutrophil and platelet engraftment was 14 (range, 11-27) and 19 days (range, 15-55), respectively, with 1 case of primary graft failure and few cardiac, renal, or hepatic events of interest. Cumulative incidence of grades 2 to 4 aGVHD by day +180 was 13% (95% confidence interval [CI] 8-20), with only 1 grade 3 to 4 case. Cumulative incidence of moderate-severe cGVHD by 12 months was 13% (95% CI 7-22). At 12 months, relapse was 18% (95% CI 10-27), NRM 5% (95% CI 2-10), PFS 77% (95% CI 66-85), and OS 84% (95% CI 74-91). PTCy 40-40 resulted in low rates of GVHD, toxicity events of interest, and NRM, with excellent 12-month PFS and OS. Our findings from this 2-center retrospective cohort analysis suggest that PTCy 40-40 is safe and effective for GVHD prophylaxis after MAC or RIC HCT from any donor type.