Engraftment of early erythroid progenitors is not delayed after non‐myeloablative major ABO‐incompatible haematopoietic stem cell transplantation

Summary. We hypothesized that patients undergoing major ABO‐incompatible non‐myeloablative haematopoietic stem cell transplantation (nm‐HSCT) might experience prolonged haemolysis after transplant due to the delayed disappearance of host plasma cells producing anti‐donor isohaemagglutinins (HAs). To address this question, we analysed data from 107 consecutive patients transplanted with allogeneic peripheral blood stem cells from human leucocyte antigen‐matched (related, n = 84; unrelated, n = 23) donors after non‐myeloablative conditioning (200 cGy total body irradiation ± fludarabine). In total, 23 out of the 107 patients received major or major/minor ABO‐incompatible transplants. Red blood cell (RBC) transfusion requirements during the first 120 d post transplant were higher in major ABO‐mismatched than in ABO‐matched recipients (0·12 vs 0·03 median units RBC concentrate/d, P = 0·04). Two patients developed transient pure red cell aplasia, which had resolved spontaneously by 9 months after transplant. Major ABO incompatibility did not influence rates of engraftment. Patients with sustained engraftment experienced gradual declines of anti‐donor HAs, and the estimated median time to reaching IgM and IgG titres of < 1:1 was at least 133 d in evaluable patients, approximately twice longer than reported after myeloablative conditioning. There was a strong correlation between degrees of donor chimaerism in erythroid burst‐forming units, granulocyte macrophage colony‐forming units and granulocytes, indicating that donor erythroid engraftment, defined by early erythroid progenitors, was as prompt as myeloid engraftment. In conclusion, our data suggest that major ABO‐incompatibility is not a barrier to successful non‐myeloablative HSCT.