THE USE OF MYCOPHENOLATE MOFETIL (RS-61443) IN HUMAN HEART-TRANSPLANTRECIPIENTS

Mycophenolate mofetil is a potent inhibitor of de novo guanine nucleot ide synthesis that selectively blocks lymphocyte proliferative respons es. In animal models, mycophenolate mofetil has been shown to prolong allograft survival, reverse ongoing rejection, and induce strain-speci fic tolerance. To assess the safety and efficacy of mycophenolate mofe til in cardiac transplantation, 30 recipients with mild rejection were enrolled in an 8-week phase I trial. Mycophenolate mofetil in doses f rom 500 to 3000 mg/day orally was substituted for azathioprine, while baseline cyclosporine levels and cortico-steroid doses were maintained . Rejection resolved in the majority of patients, with a significant d ecrease in mean biopsy score. By protocol, mycophenolate mofetil was d iscontinued in 4 patients due to persistent mild rejection, and in 4 p atients due to progression to moderate rejection. The rate of progress ion to moderate rejection compared favorably with that observed in pat ients with mild rejection maintained on azathioprine without augmentat ion of immunosuppression. Significant increases were observed in hemat ocrit, total white blood cell count, and absolute neutrophil count. Ab solute lymphocyte count remained unchanged. No nephrotoxicity or hepat otoxicity was observed. Gastrointestinal side effects prompted discont inuation of mycophenolate mofetil in one patient. Two major infections occurred. Mycophenolate mofetil remained well tolerated during long-t erm maintenance immunosuppression, with a rate of rejection similar to that in patients receiving azathioprine. We conclude that mycophenola te mofetil is safe and well tolerated in cardiac transplant recipients , is less myelosuppressive than azathioprine, and appears to be at lea st equipotent to azathioprine.