Chronic graft-versus-host disease: clinical manifestation and therapy

Chronic graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in long-term survivors of allogeneic stein cell transplantation. The immunopathogenesis of chronic GVHD is, in part, TH-2 mediated, resultin g in a syndrome of immunodeficiency and an autoimmune disorder. The most im portant risk factor for chronic GVHD is prior history of acute GVHD and str ategies that prevent acute GVHD also decrease the risk of chronic GVHD. Oth er important risk factors are the use of a non-T cell-depleted graft, and o lder age of donor and recipient. Whether recipients of peripheral blood ste m cells are at increased risk of chronic GVHD remains unsettled. There are no known pharmacologic agents which can specifically prevent development of chronic GVHD. Agents which have efficacy in the treatment of autoimmune di sorders have been utilized as therapy for established chronic GVHD and are associated with response rates of 20% to 80%. Most responses are confined t o skin, soft tissue, oral mucosa and occasionally liver. Bronchiolitis obli terans responds infrequently to therapy and is associated with a dismal pro gnosis. Newer, promising therapeutic strategies under investigation include thalidomide, photopheresis therapy, anti-tumor necrosis factor and B cell depletion with anti-CD20 monoclonal antibody.