Pharmacologic Prevention of Acute Graft-versus-Host Disease

Early human transplants of allogeneic marrow were often complicated by graft-versus-host disease (GVHD). This chapter focuses primarily on the most frequently used drugs for immunosuppression or immunomodulation for GVHD. It discusses the pathogenesis, alloreactivity, and the predictive factors utilized as targets for agents in the prevention of GVHD. Non-specific immunosuppressive drugs Corticosteroids have been combined with other immunosuppressants in prophylaxis against GVHD, but is most frequently used as front-line therapy in the treatment of established GVHD. At the cellular level, MTX exerts its cytotoxic effect by inhibiting dihydrofolate reductase (DHFR). Methotrexate (MTX) is an analog of aminopterin, the folic acid antagonist introduced in 1948 for the treatment of acute leukemia. Specific T-cell immunosuppressive drugs Cyclosporine (CSP) is a neutral hydrophobic cyclic peptide composed of 11 amino acids. Tacrolimus is a macrolide antibiotic extracted from the soil fungus Streptomyces tsukubaensis and exhibit a similar selective immunosuppressive activity.

Duke Scholars

Author Nelson Jen An Chao Medicine, Hematologic Malignancies and Cellular Therapy