TREATMENT AND PREVENTION OF ACUTE GRAFT-VERSUSHOST DISEASE WITH THALIDOMIDE IN A RAT MODEL

Abstract

We have investigated the immunosuppressive effects of thalidomide (Thal) in a bone marrow transplant (BMT) model for graft-versus-host disease (GVHD). Lewis rats received RT1-incompatible marrow transplants from ACI rats after total-body irradiation. Twenty-two of twenty-three rats with established severe acute GVHD were successfully treated with Thal. Thal was given for therapy by gavage at 50 mg/kg/day or 100 mg/kg/day for 40 days after GVHD was clinically and histologically present. Fourteen of twenty-two received prophylaxis successfully with Thal at a dose of 50 mg/kg/day or 100 mg/kg/day. Acute GVHD did not develop after the drug was stopped. Three animals treated for severe GVHD later developed chronic GVHD. Chimerism was shown by permanent acceptance of ACI skin grafts and rejection of third-party skin grafts. Lymphocytes from Thal-treated animals like-wise did not respond to Lewis or ACI cells in mixed lymphocyte culture but responded to third-party BN lymphocytes. Thal appears to be a potent new agent for therapy and prophylaxis of GVHD.