ADMINISTRATION OF MYCOPHENOLATE MOFETIL IN A MURINE MODEL OF ACUTE GRAFT-VERSUS-HOST DISEASE AFTER BONE-MARROW TRANSPLANTATION

Background Graft-versus-host disease (GVHD) remains the most significa nt obstacle to the use of allogeneic bone marrow transplantation as a treatment for leukemia and other hematological malignancies, Because c urrent GVHD treatment regimens such as cyclosporine and methotrexate a re only partially effective, there is a need for new immunosuppressive drugs for the treatment of this condition, Methods. A recently develo ped immunosuppressive drug, mycophenolate mofetil (MM), was tested in a fully mismatched (C57BL/6 donors to BALB/c recipients) murine model of acute GVHD after bone marrow transplantation. Results, A dose regim en of 30 mg/kg/day given by oral gavage and begun at 1 day before tran splant had no positive effect on survival and was found to retard the rate of marrow engraftment as measured by absolute blood neutrophil co unts, In all subsequent experiments, treatment was begun on day 5 afte r transplant, Three different doses (30, 60, and 90 mg/kg/day) were te sted, but no significant improvement in mean survival time (MST) was o bserved for the first two doses (P=0,412 and 0.100, respectively), The highest dose (90 mg/kg/day) reduced MST (P=0,059), and no further dos e increases were attempted, MM in combination with cyclosporine also f ailed to improve MST compared with animals treated with cyclosporine a lone or controls. Conclusions, These results suggest that MM given ora lly is not effective in this murine model of GVHD and may not have a r ole in the treatment and prevention of acute GVHD arising from bone ma rrow transplantation in the clinical setting.