title: Effect of donor-recipient HLA matching at HLA A, B, C, and DRB1 on outcomes after umbilical-cord blood transplantation for leukaemia and myelodysplastic syndrome: a retrospective analysis.
abstract: BACKGROUND
  The importance of matching at the HLA C locus has not been well defined for unrelated umbilical-cord blood transplantation. The selection algorithm for umbilical-cord blood units generally considers intermediate resolution HLA typing at A and B and allele-level typing at DRB1. We aimed to establish the relative importance of additional matching at HLA C.
  
  
  METHODS
  We used Cox regression to assess retrospectively the effect of donor-recipient HLA matching on outcomes of single umbilical-cord blood transplantations for leukaemia and myelodysplastic syndrome. Our primary endpoint was transplant-related mortality. HLA typing was done with molecular techniques with a minimum of intermediate resolution for HLA A, B, and C, and at the allele-level for DRB1.
  
  
  RESULTS
  The median age of our study population was 10 years (range <1-62) and 552 (69%) of 803 patients were aged 16 years or younger at transplantation. Compared with transplantations matched at HLA A, B, C, and DRB1 (n=69), transplant-related mortality risk was higher after transplantations matched at HLA A, B, and DRB1 and mismatched at HLA C (n=23; HR 3·97, 95% CI 1·27-12·40; p=0·018). Transplant-related mortality risk was also higher after transplantations with a single mismatch at HLA A, B, or DRB1 and mismatched at HLA C (n=234; 1·70, 1·06-2·74; p=0·029) compared with transplantations matched at HLA C with a single mismatch at HLA A, B, or DRB1 (n=127). Assessing the overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (n=259; 3·27, 1·42-7·54; p=0·006), three (n=253; 3·34, 1·45-7·71; p=0·005), or four (n=75; 3·51, 1·44-8·58; p=0·006) loci compared with matched units (n=69).
  
  
  CONCLUSIONS
  Our data suggest that the present strategy for umbilical-cord blood unit selection should be reassessed; matching at HLA C for units that are matched at HLA A, B, or DRB1 or in the presence of a single locus mismatch at HLA A, B, or DRB1 should be included to minimise mortality risks.
  
  
  BACKGROUND
  National Cancer Institute, National Heart Lung and Blood Institute, National Institute for Allergy and Infectious Diseases, Leukemia and Lymphoma Society, US Department of the Navy, Children's Leukemia Research Association, and INSERM.
authors: Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI 53226, USA. meapen@mcw.edu
authors: Mary
authors: M
authors: Eapen
authors: John P
authors: JP
authors: Klein
authors: Guillermo F
authors: GF
authors: Sanz
authors: Stephen
authors: S
authors: Spellman
authors: Annalisa
authors: A
authors: Ruggeri
authors: Claudio
authors: C
authors: Anasetti
authors: Maria
authors: M
authors: Brown
authors: Richard E
authors: RE
authors: Champlin
authors: Joan
authors: J
authors: Garcia-Lopez
authors: Gareth
authors: G
authors: Hattersely
authors: Gesine
authors: G
authors: Koegler
authors: Mary J
authors: MJ
authors: Laughlin
authors: Gerard
authors: G
authors: Michel
authors: Samir K
authors: SK
authors: Nabhan
authors: Franklin O
authors: FO
authors: Smith
authors: Mary M
authors: MM
authors: Horowitz
authors: Eliane
authors: E
authors: Gluckman
authors: Vanderson
authors: V
authors: Rocha
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D005060:Europe; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015235:HLA-B Antigens / Q000276:immunology; D015236:HLA-C Antigens / Q000276:immunology; D059811:HLA-DRB1 Chains / Q000235:genetics / Q000276:immunology; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007938:Leukemia / Q000276:immunology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D018579:Patient Selection; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D059811:HLA-DRB1 Chains