Allogeneic hematopoietic SCT is a potentially curative treatment for patients with high-risk hematological malignancies. The major complication assqciated with this form of therapy is GVHD. GVHD is due to the alloactivation of donor T-cells, which results in the production of proinflammatory cytokines, and recruitment of other immune effector cells resulting in tissue injury. GVHD typically affects a fairly restricted set of organs (that is, skin, liver and gastrointestinal tract) during the acute phase, whereas tissue involvement is much more extensive in chronic GVHD where nearly all organs can be affected. Because of the multi-system nature of the disease, systemic treatments are invariably used to control generalized inflammation. Primary first-line treatment of GVHD is usually with systemic corticosteroids, which typically results in responses in ~50% of patients. For those patients who fail to respond there is no standard second-line therapy that has been validated in well-designed clinical trials. The majority of patients are treated with other systemic immune-suppressive therapies that target T-cell activation pathways or inflammatory cytokine production.
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