Patient interleukin-18 GCG haplotype associates with improved survival and decreased transplant-related mortality after unrelated-donor bone marrow transplantation

Sandra M.P. Cardoso, Todd E. DeFor, Louise A. Tilley, Jeffrey L. Bidwell, Daniel J. Weisdorf, Margaret L. MacMillan

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29 Scopus citations

Abstract

Interleukin-18 (IL-18), a proinflammatory cytokine, is elevated in patients with acute graft-versus-host disease (aGVHD). IL-18 induces Th1 differentiation and cytotoxic T-lymphocyte function, both of which have been implicated in the pathogenesis of aGVHD. However, recent studies have shown that neutralization of IL-18 by antibodies leads to an increased risk of aGVHD-related mortality while administration of IL-18 significantly improved survival. We have genotyped a cohort of 157 patient/donor pairs undergoing unrelated donor bone marrow transplantation (BMT) for three polymorphisms recently identified in the promoter of the IL-18 gene: G-137C, C-607A and G-656T. Using PHASE software, three main haplotypes were reconstructed: GCG, CAT and GAT. We found no association between the occurrence of aGVHD and patient/donor haplotypes. The presence of the GCG haplotype in patients was associated with significantly decreased risk of transplant-related mortality at 100 d (23% in patients with GCG vs. 48% in patients without GCG, P < 0.01) and at 1 year (36% vs. 65%, P < 0.01). The presence of the GCG haplotype in patients was also associated with improved survival (57% vs. 32%, P < 0.01). Cox regression analysis showed that the presence of the GCG haplotype was associated with a twofold increased probability of survival. These data suggest that the IL-18 promoter GCG haplotype may influence survival after unrelated donor BMT without altering the risk of aGVHD.

Original languageEnglish (US)
Pages (from-to)704-710
Number of pages7
JournalBritish journal of haematology
Volume126
Issue number5
DOIs
StatePublished - Sep 2004

Keywords

  • Acute graft-versus-host disease
  • Bone marrow transplantation
  • Haplotypes
  • Interleukin-18
  • Single nucleotide polymorphisms

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