OKT3 for treatment of rejection in renal transplantation

OKT3 is highly effective both as an initial treatment for renal allograft rejection and as a treatment for rejection episodes resistant to other agents. When compared both prospectively and retrospectively with high-dose steroids, OKT3 was reported to be more effective in the first-line treatment of renal allograft rejection. In a large multicenter randomized trial, OKT3 reversed rejection episodes in a significantly greater number of patients and produced significantly better 1-yr graft survival than did steroids. Both agents were associated with similar numbers of infections. Acute adverse reactions attributable to cytokine release followed initial doses of OKT3. In uncontrolled trials, OKT3 reversed 50% to 100% of steroid-resistant rejections; and in a comparative study, it reversed a greater number of steroid-resistant rejection episodes than did polyclonal antilymphocyte globulins. Successful First-line and second-line (steroid-resistant) OKT3 reversal of acute severe rejection has been shown to be associated with these factors: initiation of OKT3 therapy within 7 d of rejection diagnosis and cyclosporine levels above 150 ng/ml prior to initiation of treatment. Second-line treatment of steroid-resistant rejection also was shown to be most effective in histopathologically pure acute cellular rejection episodes (lacking interstitial fibrosis). As third-line therapy, OKT3 reversed rejection episodes in 74% to 84% of patients. It is unclear whether, during OKT3 treatment, cyclosporine should be discontinued to lessen its potential for nephrotoxicity and over-immunosuppression or its dosage reduced to maintain additional immunosuppression and suppression of anti-OKT3 antibody production. OKT3 has been successfully administered for the treatment of rejection on an outpatient basis, offering considerable cost savings over continued hospitalization.