PREVENTION OF THE ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) IN RATS BY THE IMMUNOMODULATING DRUG LEFLUNOMIDE

The grafting of immunocompetent allogeneic cells into MHC-discordant, genetically nonresponsive F-1 hybrids of inbred rat strains consistent ly leads to an acute, lethal graft-versus-host disease (GVHD). The nov el immunomodulating drug leflunomide, which has been shown to be effic acious in animal models of autoimmunity and adverse transplantation re actions, was studied in a rat model of GVHD. It was found that this dr ug not only was a powerful agent to prevent this otherwise terminal di sorder, but was also proficient when used as a therapy of an establish ed GVHD. Since leflunomide has been shown to be efficacious and safe i n patients with chronic rheumatoid arthritis, it would also be reasona ble to investigate this drug in clinical trials for bone marrow transp lantation and GVHD in human beings.