Incidence of and Risk Factors for Delayed Engraftment after Post-Transplant Cyclophosphamide

Prevention of graft-versus-host disease (GVHD) with post-transplant cyclophosphamide (PTCy) after allogeneic hematopoietic cell transplantation (HCT) is increasingly becoming the standard of care [1]. Although PTCy has demonstrated consistent and impressively low rates of acute and chronic GVHD, we have observed significant variability in engraftment kinetics. We conducted a single-center retrospective cohort analysis including patients receiving PTCy (50 mg/kg/d on d +3 and +4) paired with tacrolimus/MMF at Massachusetts General Hospital from February 2016 to April 2023. The primary objective was evaluation of the incidence of delayed engraftment which was defined as: (1) neutrophil engraftment occurring ≥21 d after HCT, (2) neutrophil engraftment not occurring and surviving ≥21 d after HCT, or (3) death before neutrophil engraftment. We then evaluated clinical factors associated with delayed engraftment, including post-HCT organ toxicities attributed to PTCy. We believe that patients who experience delayed engraftment, specifically those with slow neutrophil engraftment, likely experienced increased morbidity in terms of length of hospital stay, incidence of opportunistic infections, prolonged need for transfusions, and potential need for additional donor progenitor cells or second HCT. Further characterization of the incidence of delayed engraftment and any associated clinical risk factors is important for defining populations for consideration of alternative GVHD prophylaxis regimens.