Thalidomide for treatment of graft-versus-host disease.
We have used thalidomide in a rat major MHC mismatch model of graft-versus-host disease (GVHD). When given prophylactically, most animals do not develop GVHD and those developing mild GVHD respond to continued therapy. Treatment of established acute GVHD, likewise, was successful. In both prophylactic and therapeutic administration, animals did not develop GVHD after drug cessation. Animals were shown to be stable chimeras by acceptance of donor strain skin grafts and mixed lymphocyte cultures (no response to donor or recipient strain while responding to third party strain). Treatment of chronic GVHD in this model has shown thalidomide to be better tolerated and more successful than cyclosporine (CSA) or prednisone plus azathioprine. The mechanism of action of thalidomide has been explored using a fluorescent thalidomide derivative. These studies have shown striking similarities between thalidomide and CSA. Both drugs appear to allow the development of antigen specific suppressor cells while inhibiting the development of precursor cytotoxic cells. Because of these encouraging results, we have begun a phase I/II trial of thalidomide in refractory GVHD. The preliminary results are encouraging.
Vogelsang
G B
GB
Johns Hopkins Hospital, Baltimore, MD 21205.
Hess
A D
AD
Santos
G W
GW
D000818:Animals; D016026:Bone Marrow Transplantation; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents; D051381:Rats; D013792:Thalidomide / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D013792:Thalidomide