Reduced-Dose Post-Transplant Cyclophosphamide as Graft-Versus-Host Disease Prophylaxis in Matched Donor Allogeneic Stem Cell Transplantation: A Systematic Review of Efficacy and Toxicity.

The standard 100 mg/kg dose of post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis after matched allogeneic stem cell transplantation (ASCT) is associated with important toxicities, such as infections, hemorrhagic cystitis, and cardiotoxicity. Dose reduction may ameliorate toxicities while preserving GVHD control. MEDLINE, Embase, Cochrane CENTRAL, and Google Scholar were systematically searched for studies evaluating reduced-dose PTCy (<100 mg/kg) in matched-related (MRD)/matched-unrelated donor (MUD) ASCT and reporting GVHD outcomes, survival, engraftment, and/or cardiotoxicity. Risk of bias (ROB) was assessed using RoB 2.0 for randomized controlled trials (RCTs) and ROBINS-I for non-randomized comparative studies. Eighteen studies were included. Dose reduction of PTCy ranged from 40 mg/kg to 80 mg/kg. Reduced-dose PTCy showed similar rates of acute and chronic GVHD compared to controls. Five of 8 non-randomized comparative studies had a critical ROB. The single RCT demonstrated significantly lower acute and chronic GVHD with 40 mg/kg PTCy plus reduced-dose ATG and had some concerns of bias. Recipients of reduced-dose PTCy reported lower rates of cytomegalovirus reactivation and hemorrhagic cystitis, and accelerated neutrophil and platelet engraftment. Current evidence on reduced-dose PTCy in matched ASCT is limited by observational data at high risk of bias and lack of consensus on what constitutes appropriate dose reduction. Nevertheless, these data demonstrate the feasibility of reduced-dose PTCy and are supportive of future RCTs.