Failure of cyclosporine to induce graft-vs-host disease or graft-vs-leukemia after syngeneic bone marrow transplantation in mice

Abstract

Cyclosporine administration can result in graft-vs-host disease (GVHD) after syngeneic or autologous bone marrow transplantation (BMT). However, data on its anti-tumor effects are limited. We have tried to produce cyclosporine-induced GVHD or graft-vs-leukemia (GVL) against two la-bearing murine leukemias. BALB/c mice undergoing syngeneic BMT after total-body irradiation received 1 mg/kg or 10 mg/kg cyclosporine or dextrose intraperitoneally for 30 days post-transplant, followed by 5 × 10 3 BCL1 murine leukemia cells 1 or 3 weeks after stopping cyclosporine. Similarly, SJL/J mice undergoing syngeneic BMT received 10 mg/kg cyclosporine or dextrose intraperitoneally for 30 days post-transplant, and were inoculated with 5 × 10 3 or 10 5 murine acute myeloid leukemia (mAML) cells 3 weeks after stopping cyclosporine. No clinical or histological evidence of GVHD was seen, and leukemia-free and overall survival was similar with cyclosporine and dextrose. We conclude that under the experimental conditions used, it is not possible to induce syngeneic GVHD with cyclosporine in BALB/c or SJL/J mice. In the absence of GVHD, this approach is also not associated with any GVL effect against murine leukemias BCL1 and mAML.