PMID- 15327523
OWN - NLM
STAT- MEDLINE
DCOM- 20041101
LR  - 20081121
IS  - 0007-1048 (Print)
IS  - 0007-1048 (Linking)
VI  - 126
IP  - 5
DP  - 2004 Sep
TI  - Patient interleukin-18 GCG haplotype associates with improved survival and 
      decreased transplant-related mortality after unrelated-donor bone marrow 
      transplantation.
PG  - 704-10
AB  - 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.
FAU - Cardoso, Sandra M P
AU  - Cardoso SM
AD  - Department of Pathology and Microbiology, University of Bristol, Homeopathic 
      Hospital Site, Cotham, University Walk, Bristol BS8 1TD, UK. 
      s.pinto-cardoso@bristol.ac.uk
FAU - DeFor, Todd E
AU  - DeFor TE
FAU - Tilley, Louise A
AU  - Tilley LA
FAU - Bidwell, Jeffrey L
AU  - Bidwell JL
FAU - Weisdorf, Daniel J
AU  - Weisdorf DJ
FAU - MacMillan, Margaret L
AU  - MacMillan ML
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Haematol
JT  - British journal of haematology
JID - 0372544
RN  - 0 (Interleukin-18)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Bone Marrow Transplantation/*mortality
MH  - Female
MH  - Haplotypes
MH  - Humans
MH  - Immunophenotyping
MH  - Interleukin-18/*genetics
MH  - Living Donors
MH  - Male
MH  - *Polymorphism, Genetic
MH  - *Promoter Regions, Genetic
MH  - Regression Analysis
MH  - Risk
MH  - Transplantation, Homologous
MH  - Treatment Outcome
EDAT- 2004/08/26 05:00
MHDA- 2004/11/02 09:00
CRDT- 2004/08/26 05:00
PHST- 2004/08/26 05:00 [pubmed]
PHST- 2004/11/02 09:00 [medline]
PHST- 2004/08/26 05:00 [entrez]
AID - BJH5128 [pii]
AID - 10.1111/j.1365-2141.2004.05128.x [doi]
PST - ppublish
SO  - Br J Haematol. 2004 Sep;126(5):704-10. doi: 10.1111/j.1365-2141.2004.05128.x.