Allogeneic hematopoietic cell transplantation (HCT) provides a curative therapeutic option for a number of hematologic diseases. HLA mismatch has been associated with increased risks of acute graft versus host disease and inferior overall survival (OS), which nowadays can be overcome by utilizing post transplantation cyclophosphamide. Yet, a significant hinderance can occur, when the patient has developed antibodies (Ab’s) against donor HLA mismatched antigens, that can cause graft rejection and engraftment failure. This session will focus on the pathobiology of donor directed HLA Ab’s, on their clinical implications for the risk of rejection, and on current and novel Ab depletion strategies. Major ABO donor / recipient mismatch associates with impaired engraftment, prolonged hemolysis and inferior OS. This session will focus on the pathobiology of ABO mismatches, will emphasize their clinical implications for clinical outcomes, including novel strategies beyond steroids and rituximab.