Drug Therapy for Acute Graft-Versus-Host Disease Prophylaxis

Abstract

The mechanisms of many immunosuppressive drugs have been defined, allowing for a rational aproach to the use of these agents in GVHD prophylaxis. In addition to standard drugs such as methotrexate, cyclosporine, tacrolimus, and glucocorticoids, new agents—mycophenolate mofetil, tresperimus, rapamycin, basiliximab, and daclizumab—are now part of the immunosuppressive armamentarium. Improved understanding of tolerance has resulted in new approaches to prevention of GVHD. Anti-CD40L, CTLA-4-Ig, tresperimus, and rapamycin are agents that are being explored in this area and have shown impressive results in animal models. Currently, the standard therapy for acute GVHD prophylaxis in matched sibling transplants remains cyclosporine and methotrexate. Lower dose methotrexate, particularly in combination with tacrolimus, has shown good results in single arm studies with low toxicity, but this has not been tested in a randomized study. For unrelated donor transplants there is less GVHD when tacrolimus, rather than cyclosporine, is combined with methotrexate; there seems little reason to use cyclosporine in this setting. GVHD is still the major barrier to more widespread use of unrelated donor transplants and improved regimens are needed. In vivo T-cell depletion using Campath-1 or ATG is being used in high-risk patients. Data on its efficacy are so far anecdotal. Due to the variation in grading of GVHD between centers, randomized studies are needed to quantify the relative merits of different regimens, and participation in such studies is encouraged.