title: Effect of tolerance to noninherited maternal antigens on the occurrence of graft-versus-host disease after bone marrow transplantation from a parent or an HLA-haploidentical sibling.
abstract: In haploidentical transplantation, the mismatched haplotype of the donor can originate from either of the parents. We refer to such mismatched haplotypes as noninherited maternal antigens (NIMA haplotype) or noninherited paternal antigens (NIPA haplotype). To determine whether exposure to maternal HLA antigens benefits patients undergoing bone marrow transplantation, we analyzed graft failure and graft-versus-host disease (GVHD) after transplantations from parental or haploidentical sibling donors. We studied 269 patients receiving 1 or 2 HLA-A, -B, -DR antigen-mismatched sibling or parental non-T-cell-depleted bone marrow transplants for acute myelogenous leukemia, acute lymphoblastic leukemia, or chronic myelogenous leukemia between 1985 and 1997 that were reported to the International Bone Marrow Transplant Registry. Included were 121 (45%) NIMA-mismatched and 148 (55%) NIPA-mismatched transplantations. Sixty-three (52%) of the NIMA-mismatched transplants and 69 (47%) of the NIPA-mismatched transplants were from haploidentical sibling donors. Sibling transplantations mismatched for NIMA had similar rates of graft failure but lower rates of acute GVHD (P <.02) than NIPA-mismatched sibling transplantations. In the first 4 months after transplantation, mother-to-child transplantations involved significantly less chronic GVHD than father-to-child transplantations (P <.02). Treatment-related mortality (TRM) was significantly higher after parental transplantations (P =.009 for mother; P =.03 for father) than after haploidentical sibling transplantations mismatched for the NIMA. Non-T-cell-depleted bone marrow transplants donated by haploidentical siblings to recipients mismatched for NIPA and transplants donated by parents caused more acute and chronic GVHD and TRM than transplants donated by haploidentical siblings mismatched for NIMA.
authors.affiliation: Leiden University Medical Center, The Netherlands.
authors.forename: Jon J
authors.initials: JJ
authors.lastname: van Rood
authors.forename: Fausto R
authors.initials: FR
authors.lastname: Loberiza
authors.forename: Mei-Jie
authors.initials: MJ
authors.lastname: Zhang
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.forename: Frans
authors.initials: F
authors.lastname: Claas
authors.forename: Mitchell S
authors.initials: MS
authors.lastname: Cairo
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Robert Peter
authors.initials: RP
authors.lastname: Gale
authors.forename: Olle
authors.initials: O
authors.lastname: Ringdén
authors.forename: Jill M
authors.initials: JM
authors.lastname: Hows
authors.forename: Mary H
authors.initials: MH
authors.lastname: Horowitz
mesh_terms: D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000276:immunology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology* / Q000401:mortality; D006680:HLA Antigens / Q000276:immunology*; D006239:Haplotypes / Q000276:immunology; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D015994:Incidence; D007223:Infant; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D008875:Middle Aged; D009679:Nuclear Family; D011247:Pregnancy; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000276:immunology / Q000401:mortality
chemical_list: D006680:HLA Antigens