title: Persistence of recipient plasma cells and anti-donor isohaemagglutinins in patients with delayed donor erythropoiesis after major ABO incompatible non-myeloablative haematopoietic cell transplantation.
abstract: Delayed donor erythropoiesis and pure red-cell aplasia (PRCA) complicate major-ABO mismatched non-myeloablative allogeneic stem-cell transplantation. To characterize these events, we analysed red-cell serology and chimaerism in lymphohaematopoietic lineages, including plasma cells and B cells, in 12 consecutive major-ABO incompatible transplants following cyclophosphamide/fludarabine-based conditioning. Donor erythropoiesis was delayed to more than 100 days in nine (75%) patients including six (50%) who developed PRCA. During PRCA, all patients had persistent anti-donor isohaemagglutinins and recipient plasma cells (5-42%), while myeloid and T cells were completely donor in origin. In contrast, B-cell chimaerism was frequently full-donor when significant anti-donor isohaemagglutinins persisted. Four patients with early mixed haematopoietic chimaerism and the prolonged presence of anti-donor isohaemagglutinins and recipient plasma cells developed delayed-onset (>100 days post-transplant) red cell transfusion dependence and PRCA after myeloid chimaerism converted from mixed to full donor. These findings confirm that donor-erythropoiesis is impacted by temporal disparities in donor immune-mediated eradication of recipient lymphohaematopoietic cells during major-ABO incompatibility and suggest that plasma cells are relatively resistant to graft-versus-host haematopoietic effects.
authors.affiliation: Department of Transfusion Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1652, USA.
authors.forename: L M
authors.initials: LM
authors.lastname: Griffith
authors.forename: J P
authors.initials: JP
authors.lastname: McCoy
authors.forename: C D
authors.initials: CD
authors.lastname: Bolan
authors.forename: D F
authors.initials: DF
authors.lastname: Stroncek
authors.forename: A C
authors.initials: AC
authors.lastname: Pickett
authors.forename: G F
authors.initials: GF
authors.lastname: Linton
authors.forename: A
authors.initials: A
authors.lastname: Lundqvist
authors.forename: R
authors.initials: R
authors.lastname: Srinivasan
authors.forename: S F
authors.initials: SF
authors.lastname: Leitman
authors.forename: R W
authors.initials: RW
authors.lastname: Childs
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000276:immunology / Q000601:surgery; D001402:B-Lymphocytes / Q000502:physiology; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000276:immunology / Q000601:surgery; D004920:Erythropoiesis; D005260:Female; D006388:Hemagglutinins; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000276:immunology / Q000601:surgery; D008297:Male; D008545:Melanoma / Q000097:blood / Q000276:immunology / Q000601:surgery; D008565:Membrane Proteins / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000276:immunology / Q000601:surgery; D009369:Neoplasms / Q000097:blood / Q000276:immunology / Q000601:surgery*; D010950:Plasma Cells; D012010:Red-Cell Aplasia, Pure / Q000097:blood* / Q000276:immunology; D012878:Skin Neoplasms / Q000097:blood / Q000276:immunology / Q000601:surgery; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D018183:Transplantation Chimera / Q000097:blood / Q000276:immunology; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous
chemical_list: D006388:Hemagglutinins; D008565:Membrane Proteins; C080086:phosphatidylinositol glycan-class A protein