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Related Collections Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 11 (December 1), 1999: pp. 3941-3946 Recipient Tumor Necrosis Factor- and Interleukin-10 Gene Polymorphisms Associate With Early Mortality and Acute Graft-Versus-Host Disease Severity in HLA-Matched Sibling Bone Marrow Transplants James Cavet, Peter G. Middleton, Miriam Segall, Harriet Noreen, Stella M. Davies, and Anne M. Dickinson From the University Department of Haematology, School of Clinical and Laboratory Sciences, The Medical School, University of Newcastle Upon Tyne, Newcastle Upon Tyne, UK; and the Department of Bone Marrow Transplantation and Clinical Research, University of Minnesota, Minneapolis, MN. The proinflammatory cytokine tumor necrosis factor- (TNF-) is strongly implicated in graft-versus-host disease (GVHD) and other acute bone marrow transplant (BMT) complications. The antiinflammatory interleukin-10 (IL-10) antagonizes TNF- and reduces GVHD. We previously showed association of recipient TNF (TNFd) and IL-10 (IL-101064) gene polymorphisms with acute GVHD severity in matched sibling BMT using only cyclosporin A monotherapy. The current study tested association of GVHD with TNFd and IL-101064/-1082 polymorphisms in a large cohort (144 matched sibling donor/recipient pairs) given both cyclosporine A (CyA) and methotrexate (MTX) prophylaxis. Genotype results were correlated with acute and chronic GVHD and mortality. Patients homozygous for the TNFd microsatellite allele 3 had higher early mortality: 23.7% of TNFd3/d3 homozygotes died before day 30, compared with 6.80% of non-d3/d3 recipients (P = .013). Recipients possessing longer IL-101064 microsatellite alleles developed more severe acute GVHD: 22.3% of recipients possessing alleles 12 to 15 developed grade III to IV GVHD, versus 3.92% of those with smaller alleles (P < .01). Other recipient or donor genotypes tested did not significantly affect GVHD or mortality. We conclude that recipient TNFd and IL-101064 polymorphisms associate with early mortality and severe acute GVHD in matched sibling BMT with dual prophyaxis. This supports the hypothesis of genetic predisposition towards GVHD and other BMT complications other than histocompatibility antigen disparity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. Socie and B. R. Blazar Acute graft-versus-host disease: from the bench to the bedside Blood, November 12, 2009; 114(20): 4327 - 4336. [Abstract] [Full Text] [PDF] K.-H. Lee, S. S. Park, I. Kim, J. H. Kim, E. K. Ra, S.-S. Yoon, Y.-C. Hong, S. Park, and B. K. Kim P2X7 receptor polymorphism and clinical outcomes in HLA-matched sibling allogeneic hematopoietic stem cell transplantation Haematologica, May 1, 2007; 92(5): 651 - 657. [Abstract] [Full Text] [PDF] M. 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