title: In a 12-allele analysis HLA-DPB1 matching is associated with improved OS in leukaemic and myelodysplastic patients receiving myeloablative T-cell-depleted PBSCT from unrelated donors.
abstract: The effect on survival of including HLA-DPB1 in a 12-allele matching strategy was retrospectively evaluated in 130 patients with acute leukaemia and myelodysplasia undergoing T-cell-depleted PBSC transplantation using unrelated donors. Patients received alemtuzumab in vivo T-cell depletion as part of a myeloablative (MA; n=61) or reduced-intensity conditioning regimen (n=69). No difference in OS was seen with single-locus mismatching (mm) when 10 conventional alleles (HLA-A, B, C, DRB1 and DQB1) were considered. However, the addition of HLA-DPB1 matching data proved highly discriminatory. Mismatches were identified in 87% of patients previously considered fully matched (1DPmm=49pts: 2DPmm=28pts), and in the 9/10 group 22 patients were reclassified as double and 16 as triple mismatches. In 10/10 transplants, there was a distinct trend to poorer OS with double DPB1 mm. If all 12 loci were considered, 98% of single mm were at HLA-DPB1. Furthermore, cumulative mm at two or more loci was associated with significantly poorer 3-year OS (34% vs 48%, P=0.013: hazard ratio 1.8 (95% confidence interval 1.14-3.06; P=0.017), although his detrimental effect was only apparent using MA conditioning, in which reduced OS was associated with increased chronic GVHD (61% vs 16%, P=0.018) and nonrelapse mortality (30% vs 9%, P=0.039).
authors.affiliation: Histocompatibility and Immunogenetics Laboratory, Gartnavel General Hospital, Glasgow, UK.
authors.forename: C
authors.initials: C
authors.lastname: Burt
authors.affiliation: Blood and Marrow Stem Cell Transplant Unit, Beatson, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK.
authors.forename: A
authors.initials: A
authors.lastname: Parker
authors.affiliation: Blood and Marrow Stem Cell Transplant Unit, Beatson, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK.
authors.forename: G
authors.initials: G
authors.lastname: McQuaker
authors.affiliation: 1] Blood and Marrow Stem Cell Transplant Unit, Beatson, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK [2] Paul O'Gorman Research Laboratories, University of Glasgow, Glasgow, UK [3] College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: M
authors.initials: M
authors.lastname: Copland
authors.affiliation: Haematology Department, Western General Hospital, Edinburgh, UK.
authors.forename: C
authors.initials: C
authors.lastname: Brierley
authors.affiliation: 1] Histocompatibility and Immunogenetics Laboratory, Gartnavel General Hospital, Glasgow, UK [2] College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: A-M
authors.initials: AM
authors.lastname: Little
authors.affiliation: Blood and Marrow Stem Cell Transplant Unit, Beatson, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK.
authors.forename: A
authors.initials: A
authors.lastname: Clark
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D005260:Female; D059868:HLA-DP beta-Chains / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D008212:Lymphocyte Depletion / Q000379:methods* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019653:Myeloablative Agonists / Q000008:administration & dosage; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D019172:Transplantation Conditioning / Q000379:methods; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D019653:Myeloablative Agonists; D000074323:Alemtuzumab