A RANDOMIZED PROSPECTIVE-STUDY COMPARING LOW-DOSE OKT3 TO LOW-DOSE ATG FOR THE TREATMENT OF ACUTE STEROID-RESISTANT REJECTION EPISODES IN KIDNEY-TRANSPLANT RECIPIENTS

Acute steroid-resistant rejection episodes in kidney allograft recipie nts require treatment with antilymphocyte antibodies. Monoclonal anti- CD3 and polyclonal antilymphocyte antibodies have been widely used but seldom compared. Recent data have suggested that these antibodies cou ld be used at reduced doses without jeopardizing their efficacy. In th is study, we randomized renal transplant recipients who encountered a first acute steroid-resistant rejection episode to low-dose ATG or low -dose OKT3 treatment. Sixty patients were enrolled in the study. They received prophylactic immunosuppression with cyclosporin, azathioprine , and prednisolone. Treatment of biopsy-proven rejection consisted of a 10-day course of either ATG (n = 31) or OKT3 (n = 29). The total ATG dose was 484 +/- 110 mg, i.e., 0.75 mg/kg per day. The total OKT3 dos e was 32 +/- 4 mg, i.e., 0.05 mg/kg per day. We compared reversion of rejection, side effects, immunodepression, and graft function. Reversi on of rejection was similar in the two groups, although we noted a tre nd in favor of ATG. Results were 3 % vs 10 % early graft failures, 13 % vs 23 % overall graft failures, 28 % vs 38 % 3-month actuarial incid ence of rebound rejection, and 89 % vs 81 % 1-year graft survival rate in the ATG and OKT3 groups, respectively. Tolerance was worse in the OKT3 group due to the first-dose syndrome. Infections and cancers occu rred with the same frequency. ATG resulted in a deeper and longer decr ease in peripheral lymphocyte subsets. Graft function was similar in t he two groups. We conclude that low-dose ATG and low-dose OKT3 are equ ally effective in reversing steroid-resistant acute rejection. Toleran ce was better with ATG, which also gave a more potent and longlasting immunodepression. The use of reduced doses of ATG and OKT3 did not app ear to lessen their efficacy.