Acute and chronic graft-versus-host disease: clinical manifestations, prophylaxis, and treatment

Graft-versus-host disease (GvHD) is a clinical syndrome observed in recipients of allogeneic marrow grafts, presumably due to an attack of donor T-lymphocytes against host (patient) tissue. Acute GvHD develops within the first 2-3 months of transplantation and occurs in 25-60% of recipients of HLA genotypically identical transplants. The major target organs are skin, liver, intestinal tract, and conjunctivae. About one-half of the patients with moderately severe to severe GvHD die, generally from associated infections. Attempts at prevention of acute GvHD, such as selection of HLA-identical donors, postgrafting immunosuppression, decontamination of the patient and placement in a sterile environment, or T-cell depletion of the donor marrow, have met with only partial success. Treatment of established GvHD involves the use of immunosuppressants, such as steroids, antithymocyte globulin, cyclosporine, and monoclonal antibodies. Chronic GvHD generally develops 3 months to 1 year after grafting and affects 40-45% of surviving patients. Target organs, in addition to those of acute GvHD, include exocrine glands and mucous and serous membranes. The clinical picture strongly resembles collagen vascular diseases. Chronic GvHD occurs more frequently in older patients and patients with preceding acute GvHD. These patients are susceptible to bacterial or fungal infections that may be fatal. Treatment of chronic GvHD involves the use of immunosuppressive and cytotoxic drugs and prophylactic antibodies.