title: Engraftment of early erythroid progenitors is not delayed after non-myeloablative major ABO-incompatible haematopoietic stem cell transplantation.
abstract: 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.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: J
authors.initials: J
authors.lastname: Maciej Zaucha
authors.forename: Marco
authors.initials: M
authors.lastname: Mielcarek
authors.forename: Alessandra
authors.initials: A
authors.lastname: Takatu
authors.forename: Marie-Terese
authors.initials: MT
authors.lastname: Little
authors.forename: Theodore
authors.initials: T
authors.lastname: Gooley
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baker
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.forename: Michael
authors.initials: M
authors.lastname: Maris
authors.forename: Thomas
authors.initials: T
authors.lastname: Chauncey
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Beverly
authors.initials: B
authors.lastname: Torok-Storb
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D000368:Aged; D001787:Blood Group Incompatibility / Q000209:etiology*; D002648:Child; D002675:Child, Preschool; D017707:Erythrocyte Transfusion / Q000706:statistics & numerical data; D015672:Erythroid Precursor Cells; D006085:Graft Survival; D006388:Hemagglutinins / Q000097:blood; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008875:Middle Aged; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous
chemical_list: D000017:ABO Blood-Group System; D006388:Hemagglutinins; D007074:Immunoglobulin G; D007075:Immunoglobulin M