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Lookup NU author(s): Dr Jennifer Cavet, Dr Peter Middleton, Professor Anne Dickinson
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The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) 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-alpha and reduces GVHD. We previously showed association of recipient TNF (TNFd) and IL-10 (IL-10(-1064)) 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-10(-1064/-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-10-1064 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-10(-1064) 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. (C) 1999 by The American Society of Hematology.
Author(s): Cavet J, Middleton PG, Segall M, Noreen H, Davies SM, Dickinson AM
Publication type: Article
Publication status: Published
Journal: Blood
Year: 1999
Volume: 94
Issue: 11
Pages: 3941-3946
Print publication date: 01/12/1999
ISSN (print): 0006-4971
ISSN (electronic): 1528-0020
Publisher: American Society of Hematology
