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 |
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| Authors: | Eapen Mary,Klein John P,Sanz Guillermo F,Spellman Stephen,Ruggeri Annalisa,Anasetti Claudio,Brown Maria,Champlin Richard E,Garcia-Lopez Joan,Hattersely Gareth,Koegler Gesine,Laughlin Mary J,Michel Gerard,Nabhan Samir K,Smith Franklin O,Horowitz Mary M,Gluckman Eliane,Rocha Vanderson Eurocord-European Group for Blood Marrow Transplantation Netcord Center for International Blood Marrow Transplant Research |
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| Affiliation: | aCenter for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI, USA;bHospital Universitario La Fe, Valencia, Spain;cCenter for International Blood and Marrow Transplant Research, National Marrow Donor Program, Minneapolis, MN, USA;dEurocord, Hôpital Saint-Louis, Paris, France;eLee Moffitt Cancer Center, Tampa, FL, USA;fMD Anderson Cancer Center, University of Texas, Houston, TX, USA;gTissue and Cell Therapeutics Centre, Barcelona Cord Blood Bank, Barcelona, Spain;hUniversity of Düsseldorf, Düsseldorf, Germany;iUniversity of Virginia Health Systems, Charlottesville, VA, USA;jUniversity Hospital of Marseille, Marseille, France;kCincinnati Children's Medical Center, University of Cincinnati Medical School, Cincinnati, OH, USA;lSirio Libanes Hospital and Cancer Children's Hospital (ITACI), University of São Paulo, Brazil |
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| Abstract: | BackgroundThe 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.MethodsWe 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.FindingsThe 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).InterpretationOur 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.FundingNational 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. |
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