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Transplantation. 2001 Aug 27;72(4):699-706.

Both genetic and clinical factors predict the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

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  • 1Service d'Hématologie Greffe de Moelle, Unité Propre d'Enseignement Supérieur UPRES EA 2378 / Université Paris VII, France. gsocie@chu-stlouis.fr

Abstract

BACKGROUND:

Graft-versus-host disease is the main complication of hematopoietic stem cell transplantation. Recently, pro- and anti-inflammatory cytokines and mismatches of minor histocompatibility antigens between HLA-identical sibling donor/recipient pairs have been implicated in the development of acute graft-versus-host disease. It is not known, however, whether these factors are independent of other clinically recognized risk factors such as age and disease stage.

METHODS:

In this study, we searched for risk factors of acute graft-versus-host disease using multivariate Cox regression analysis in 100 consecutive patients who underwent allogeneic stem cell transplantation from an HLA-identical sibling donor. Eight polymorphisms from five different cytokine genes were studied (tumor necrosis factor alpha, tumor necrosis factor beta, interleukin (IL) 6, IL-10, and interferon gamma). Mismatches for the minor histocompatibility antigen HA-1 were searched in HLA-A*0201 individuals. In addition to these new risk factors, patient, donor, disease, and transplant risk factors were analyzed by multivariate analysis using the Cox proportional hazards model.

RESULTS:

Acute graft-versus-host disease was independently associated with IL-10 gene polymorphisms both from the recipient (relative risk=7.9, P<0.0001) and the donor (relative risk=3.5, P=0.02), a donor's positive serology for cytomegalovirus, and HA-1 mismatches in HLA-A*0201 individuals (relative risk=2.8, P=0.05). Chronic graft-versus-host disease was independently associated with IL-6 gene polymorphism from the recipient (relative risk=4.2, P=0.02), older age (relative risk=2.5, P=0.0009), and previous acute graft-versus-host disease (relative risk=9.7, P=0.003).

CONCLUSION:

In addition to previously described clinical risk factors, genetic risk factors are independently associated with the risk of developing graft-versus-host disease and may, thus, be considered for the selection of the donor.

PMID:
11544434
[PubMed - indexed for MEDLINE]
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