title: Highly diverged MHC class I mismatches are acceptable for haematopoietic stem cell transplantation.
abstract: A fully major histocompatilbility complex (MHC) matched donor is not available for the majority of patients in need of a haematopoietic stem cell transplantation (SCT), which illustrates the need for a tool to define acceptable MHC disparities. Previously, we noticed that a variety of single MHC class I mismatched allogeneic donor-recipient pairs did not elicit an allogeneic cytotoxic-lymphocyte (CTL) response in vitro if the MHC amino-acid sequences had five or more differences in the alpha-helices plus five or more differences in the beta-sheet (> or =5alpha5beta) (7). To address the clinical relevance of this observation, we analysed CTL precursor (CTLp) assay outcome and SCT outcome in 53 Dutch recipients of a single MHC class I mismatched graft from an unrelated donor. Overall patient survival was 44% after 4 years. In multivariate analysis, recipients of a > or =5alpha5beta mismatched graft with negative CTLp frequencies in vitro before transplantation demonstrated superior survival: survival at 4 years was 80% as compared to 47% in recipients of other mismatched grafts with negative CTLp frequencies (hazard ratio=0.131; 95% CI=(0.03-0.61); P=0.009). This option of acceptable mismatches may enlarge the pool of potentially acceptable stem cell donors.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. M.B.A.Heemskerk@lumc.nl
authors.forename: M B A
authors.initials: MB
authors.lastname: Heemskerk
authors.forename: J J
authors.initials: JJ
authors.lastname: Cornelissen
authors.forename: D L
authors.initials: DL
authors.lastname: Roelen
authors.forename: J J
authors.initials: JJ
authors.lastname: van Rood
authors.forename: F H J
authors.initials: FH
authors.lastname: Claas
authors.forename: I I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: M
authors.initials: M
authors.lastname: Oudshoorn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D046148:Donor Selection; D005260:Female; D005500:Follow-Up Studies; D030342:Genetic Diseases, Inborn / Q000401:mortality / Q000628:therapy; D006402:Hematologic Diseases / Q000276:immunology / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality; D006648:Histocompatibility / Q000235:genetics; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007223:Infant; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D017433:Protein Structure, Secondary; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D015395:Histocompatibility Antigens Class I