Safety and feasibility of intermediate-dose post-transplant cyclophosphamide for graft-versus-host disease prophylaxis

Post-transplant cyclophosphamide (PTCy) is widely used for graft-versus-host disease (GVHD) prophylaxis in allogeneic hematopoietic stem-cell transplant (HSCT). However, the optimal dosing of PTCy remains uncertain. In this case series, we evaluated intermediate-dose PTCy (25–30 mg/kg/day on Days 3 and 4) in 11 consecutive patients treated at our center between February 2023 and November 2024. Outcomes regarding engraftment were compared to our center’s historical cohort, which received standard-dose PTCy. All 11 patients achieved neutrophil engraftment, and 10 achieved platelet engraftment. Median times to neutrophil, platelet, and lymphocyte engraftment were Day 14, 17, and 21, respectively—significantly shorter than in the standard-dose group (Day 18, 23, and 40; p < 0.05 for all comparisons, Mann–Whitney U test). Complete donor chimerism was observed in all patients by Day 30. Compared to our center’s historical cohort, significantly more patients in the intermediate-dose group achieved complete donor chimerism in both total cells and T cells (p < 0.01 and p = 0.03, respectively; Fisher’s exact test). Among the 11 patients, acute GVHD occurred in 3 patients (one each of grade I, II, and III); two of those 3 developed severe chronic GVHD. One patient died from diffuse alveolar hemorrhage; the others remain alive without relapse. Intermediate-dose PTCy demonstrated favorable engraftment, high donor chimerism, and acceptable toxicity, suggesting it may be a viable option for GVHD prophylaxis, particularly in vulnerable populations such as elderly patients, those with poor performance status, comorbidities, or splenomegaly. Larger prospective studies are warranted to validate these findings.