OKT3 FOR TREATMENT OF REJECTION IN RENAL-TRANSPLANTATION

OKT3 is highly effective both as an initial treatment for renal allogr aft rejection and as a treatment for rejection episodes resistant to o ther agents. When compared both prospectively and retrospectively wit high-dose steroids, OKT3 was reported to be more effective in the firs t-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 graf t survival than did steroids. Both agents were associated with similar numbers of infections. Acute adverse reactions attributable to cytoki ne release followed initial doses of OKT3. In uncontrolled trials, OKT 3 reversed 50% to 100% of steroid-resistant rejections; and in a compa rative study, it reversed a greater number of steroid-resistant reject ion 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: i nitiation of OKT3 therapy within 7 d of rejection diagnosis and cyclos porine levels above 150 ng/ml prior to initiation of treatment. Second -line treatment of steroid-resistant rejection also was shown to be mo st effective in histopathologically pure acute cellular rejection epis odes (lacking interstitial fibrosis). As third-line therapy, OKT3 reve rsed rejection episodes in 74% to 84% of patients. It is unclear wheth er, during OKT3 treatment, cyclosporine should be discontinued to less en its potential for nephrotoxicity and over-immunosuppression or its dosage reduced to maintain additional immunosuppression and suppressio n of anti-OKT3 antibody production. OKT3 has been successfully adminis tered for the treatment of rejection on an outpatient basis, offering considerable cost savings over continued hospitalization.