Reduced Dose of Post-transplant Cyclophosphamide with Tacrolimus for the Prevention of Graft-versus-Host Disease in HLA-Matched Donor Peripheral Blood Stem Cell Transplants: A Prospective Pilot Study

Abstract

High-dose post-transplant cyclophosphamide (PTCY) (50 mg/kg/day, days + 3/+4) is an excellent strategy to prevent GVHD. However, its use is associated with adverse outcomes such as delayed engraftment, increased risk of infection, and cardiac complications. We prospectively evaluated PTCY at a reduced dose of 40 mg/kg/day on days + 3/+4 plus tacrolimus in 22 patients undergoing HLA-matched alloHSCT. At day + 100, the cumulative incidences of grade II-IV and III-IV acute GVHD were 18.2% and 4.5%, respectively. No grade IV acute GVHD or steroid-refractory disease was observed. The cumulative incidences of all-grade and moderate-severe chronic GVHD at 1-year were 11.4% and 6.4%, respectively. No patient died from transplant-related complications. Two-year OS and RFS were 77.1% and 58.3%, respectively. Neutrophil and platelet engraftment occurred at a median of 15 (IQR 14–16) and 16 days (IQR 12–23), respectively. No patient experienced primary graft failure. The cumulative incidences of bloodstream bacterial infections, polyomavirus BK hemorrhagic cystitis, HHV6 reactivation, CMV reactivation, and fungal infections were 13.6%, 9.1%, 9.1%, 4.6%, and 6%, respectively. Only one early cardiac event was observed. These results suggest that PTCY 40 mg/kg/day on a + 3/+4 schedule provides adequate immunosuppression to allow for engraftment and prevent clinically significant GVHD with a low toxicity profile.