INCIDENCE AND MANAGEMENT OF MYCOPHENOLATE MOFETIL ADVERSE EFFECTS IN SIMULTANEOUS KIDNEY/PANCREAS TRANSPLANT RECIPIENTS

Abstract

539 Mycophenolate mofetil (MMF) is a potent noncompetitive, reversible enzyme inhibitor of the de novo purine synthetic pathway which selectively blocks both T-and B-lymphocyte proliferation. MMF in combination with FK-506 or cyclosporine has been shown to decrease the incidence of rejection in simultaneous kidney/pancreas (SKP) transplant recipients. However, tolerability and serious adverse effects of MMF in combination with FK-506 are relatively unknown. The purpose of this study was to describe the incidence and management of adverse effects when used in combination with FK-506 in SKP transplantation. A cohort of 19 patients undergoing SKP transplantation between February 9, 1997 and September 22, 1997 received an immunosuppressive regimen consisting of FK-506, steroids, and MMF without antilymphocyte induction. Surgical technique performed included 10 (53%) with portal-enteric and 9 (47%) with systemic-bladder drainage. All patients were Caucasian and 12(63%) were male, with a mean age of 40.4 years. The incidence of acute rejection was 26%. Four patients had biopsy proven kidney rejection and one patient had biopsy proven pancreas rejection treated with ATGAM (n=3) and OKT3(n=2). One patient developed recurrent rejection responsive to steroid therapy alone. There was no graft loss due to rejection. Infectious complications included bacteremia in 10 (53%), UTI in 5 (26%), fungal infections in 3 (16%), CMV infection in 2 (11%), and other infections in 2 (11%). One patient developed post transplant lympho-proliferative disease (PTLD) 10 months post transplant. The initial dosing regimen for MMF was 1 gm BID in 9 (47%), 750 mg QID in 7 (37%), and 500 QID in 3 (16%). After these starting dosage regimens 18 (95%) patients required dosage reduction secondary to adverse effects. The reason for dosage reduction included: GI side effects in 12 (63%), leukopenia in 5 (26%), thrombocytopenia in 2 (11%), CMV in 2 (11%), and PTLD in 1 (5%). Four patients had temporary MMF withdrawal for viral infection (2 CMV, 1 EBV-lymphoma) or leukopenia for a mean of 15 days. After a mean follow-up of 6 months, 53% of patients were unable to tolerate a dose of 2 gms/day, and all patients required a QID rather than a BID dosing regimen to minimize GI toxicity. Patient and kidney/pancreas graft survival rates are 100%. Conclusion: This preliminary experience with MMF in combination with FK-506 shows efficacy in controlling rejection but dose limiting toxicity. However, the use of these agents in combination may result in additive GI side effects based on the fact that less than 50% of patients could tolerate goal doses of MMF.