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Blood, Vol. 95 No. 9 (May 1), 2000:
pp. 2754-2759
The primacy of the gastrointestinal tract as a target organ of
acute graft-versus-host disease: rationale for the use of cytokine
shields in allogeneic bone marrow transplantation
Geoffrey R. Hill and
James L. M. Ferrara
From the Mater Medical Research Institute, Brisbane, Australia, and
the Departments of Internal Medicine and Pediatrics, Division of
Hematology and Oncology, University of Michigan Cancer Center,
MI.
Acute graft-versus-host disease (GVHD), the major complication of
allogeneic bone marrow transplantation (BMT), limits the application of
this curative but toxic therapy. Studies of inflammatory pathways
involved in GVHD in animals have shown that the gastrointestinal (GI) tract plays a major role in the amplification of
systemic disease. Damage to the GI tract increases the translocation of inflammatory stimuli such as endotoxin, which promotes further inflammation and additional GI tract damage. The GI tract is therefore critical to the propagation of the "cytokine storm"
characteristic of acute GVHD. Experimental approaches to the prevention
of GVHD include reducing the damage to the GI tract by fortification of the GI mucosal barrier through novel "cytokine shields" such as IL-11 or keratinocyte growth factor. Such strategies have reduced GVHD
while preserving a graft-versus-leukemia effect in animal models, and
they now deserve formal testing in carefully designed clinical trials.
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