title: Outcome of haematopoietic stem cell transplantation in patients transplanted with matched unrelated donors vs allele-mismatched donors: a single centre study.
abstract: We studied the importance of human leucocyte antigen (HLA)-A, -B and -DRB1 high-resolution matching on the outcome of haematopoietic stem cell transplantation (HSCT) with matched unrelated donors (MUDs) vs single allele-mismatched unrelated donors. Fifty consecutive HSCT patients receiving an HLA-A, -B or -DR allele-level-mismatched unrelated graft (mmUD) were compared with a matched cohort of 100 patients with an HLA-A, -B and -DR-MUD. Rejection occurred in seven patients (14%) in the mmUD group and in four patients (4%) in the MUD group (P = 0.04), but this was mainly an effect of HLA-C mismatch. The cumulative incidence of acute graft vs host disease (GVHD) grades II-IV were 61%, 26% and 33% in the class I mmUD, class II mmUD and MUD groups, respectively. In multivariate analysis, HLA class I mismatch was associated with an increased risk of acute GVHD grades II-IV (2.09, P = 0.007) and transplant-related mortality (TRM) (1.99, P = 0.06). The 5-year overall survival was 81% in patients with a class II allele-mismatched donor compared with 52% (P = 0.025) and 50% (P = 0.017) in patients with a class I mismatch and a MUD. In multivariate analysis, HLA class II allele mismatch was associated with improved survival (3.38, P = 0.019). Relapse-free survival were 53%, 37% and 42% in patients with a class II mmUD, class I mmUD and a MUD, respectively (not significant). An HLA-C or -DQ mismatch had no significant impact on survival, TRM and relapse. In conclusion, compared with MUD, HLA class I allele mmUD had an increased risk of acute GVHD and TRM.
authors.affiliation: Department of Clinical Immunology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Hauzenberger
authors.forename: M
authors.initials: M
authors.lastname: Schaffer
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: Z
authors.initials: Z
authors.lastname: Hassan
authors.forename: B
authors.initials: B
authors.lastname: Omazic
authors.forename: J
authors.initials: J
authors.lastname: Mattsson
authors.forename: A-C
authors.initials: AC
authors.lastname: Wikström
authors.forename: M
authors.initials: M
authors.lastname: Remberger
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015234:HLA-A Antigens / Q000235:genetics* / Q000276:immunology; D015235:HLA-B Antigens / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics* / Q000276:immunology; D059811:HLA-DRB1 Chains; D018380:Hematopoietic Stem Cell Transplantation; D006648:Histocompatibility / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains