Reduced-dose PTCy as GvHD prophylaxis in MRD and MUD allo-HSCT: A systematic review of efficacy and toxicity

Results from a systematic review evaluating reduced-dose post-transplant cyclophosphamide (PTCy; <100 mg/kg) as graft-versus-host disease (GvHD) prophylaxis in matched-related donor (MRD) and matched-unrelated donor (MUD) allogeneic hematopoietic stem cell transplantation (allo-HSCT) were published in Transplantation and Cellular Therapy by Shafqat et al. The results of ten studies with a control group were included.

Key data: Reduced-dose PTCy (40–90 mg/kg) demonstrated comparable rates of acute and chronic GvHD vs controls. The single multicenter randomized controlled trial (RCT) reported lower all-grade acute (23.8% vs 40.0%; p = 0.026) and chronic (14.7% vs 26.7%; p = 0.047) GvHD and improved GvHD-free relapse-free survival (GRFS; 66.1% vs 49.3%; p = 0.032) with 40 mg/kg PTCy + reduced-dose anti-thymocyte globulin (ATG), compared with standard ATG-based prophylaxis without PTCy. Reduced-dose PTCy was associated with lower rates of cytomegalovirus (CMV) reactivation and hemorrhagic cystitis, as well as accelerated neutrophil and platelet engraftment across multiple studies. Five of eight non-randomized studies were assessed as having a critical risk of bias.

Key learning: Current evidence supports the feasibility of reduced-dose PTCy in matched-donor allo-HSCT; however, high risk of bias in observational data and the absence of a consensus definition of dose reduction preclude definitive efficacy conclusions. Future RCTs powered for GRFS and directly comparing reduced- vs standard-dose PTCy are needed.