title: Diverging effects of HLA-DPB1 matching status on outcome following unrelated donor transplantation depending on disease stage and the degree of matching for other HLA alleles.
abstract: Disease stage and recipient/donor human leukocyte antigen (HLA) matching are important determinants of outcome in transplantation using volunteer-unrelated donors (VUD). Matching for HLA-A, -B, -C, -DRB1, -DQB1 is beneficial, whereas the importance of DPB1 matching is more controversial. The impact of HLA matching status may differ dependent on disease stage. We investigated the outcome according to the degree of HLA matching at 6 loci, in 488 recipients of predominantly T-cell depleted bone marrow VUD transplants for leukaemia. Survival was significantly better in 12/12-matched transplants in those with early leukaemia (5 years: 63 versus 41% in 10/10 matched, P=0.006), but not late stage disease. Conversely, within the HLA-mismatched group (< or =9/10), there was a significant survival advantage to DPB1 mismatching (5 years: 39 versus 21% in DPB1 matched, P=0.008), particularly in late leukaemia (P=0.01), persisting in multivariate analysis (odds ratio 0.478; 95% confidence interval 0.30, 0.75; P=0.001). These novel findings suggest that the best outcome for patients with early leukaemia, with a 10/10-matched donor, is achieved by matching for DPB1. Conversely, our results suggest that in patients receiving an HLA-mismatched graft, the outcome is significantly better if they are also mismatched for DPB1. We recommend validation of these results in independent datasets.
authors.affiliation: Research Department, Anthony Nolan Research Institute, Royal Free Hospital, Pond Street, Hampstead, London NW3 2QG, UK. bshaw@doctors.org.uk
authors.forename: B E
authors.initials: BE
authors.lastname: Shaw
authors.forename: N P
authors.initials: NP
authors.lastname: Mayor
authors.forename: N H
authors.initials: NH
authors.lastname: Russell
authors.forename: J F
authors.initials: JF
authors.lastname: Apperley
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: J
authors.initials: J
authors.lastname: Cornish
authors.forename: P
authors.initials: P
authors.lastname: Darbyshire
authors.forename: M E
authors.initials: ME
authors.lastname: Ethell
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: A-M
authors.initials: AM
authors.lastname: Little
authors.forename: S
authors.initials: S
authors.lastname: Mackinnon
authors.forename: D I
authors.initials: DI
authors.lastname: Marks
authors.forename: A
authors.initials: A
authors.lastname: Pagliuca
authors.forename: K
authors.initials: K
authors.lastname: Thomson
authors.forename: S G E
authors.initials: SG
authors.lastname: Marsh
authors.forename: J A
authors.initials: JA
authors.lastname: Madrigal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology; D006680:HLA Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000276:immunology*; D059868:HLA-DP beta-Chains; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D007938:Leukemia / Q000276:immunology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D014019:Tissue Donors
chemical_list: D006680:HLA Antigens; D006682:HLA-DP Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen