SEQUENTIAL OKT3 AND CYCLOSPORINE AFTER HEART-TRANSPLANTATION - A RANDOMIZED STUDY WITH SINGLE AND CYCLIC OKT3

The incidence of cardiac allograft rejection and the occurrence of renal insufficiency in the early postoperative period were compared in patients randomly allocated to receive either sequential OKT3 plus azathioprine and cyclosporine or to cyclosporine alone. Both groups were in addition on low-dose steroids. Thirty-three patients received OKT3 and in 10 of them a second course of OKT3 was given 3 weeks thereafter, regardless of the presence or absence of allograft rejection. Cyclosporine alone was given to 33 patients also. There was no significant difference in the number of acute rejections per patient in the OKT3-versus cyclosporine-treated patients (1.33 vs 1.36), nor in the freedom from rejection at 1, 3 and 6 months: 80%, 31% and 28% vs 66%, 33% and 27% respectively. No difference in freedom from rejection was found between patients who received single versus cyclic doses of OKT3. In the OKT3-treated patients there were no nephrological problems. In the cyclosporine group median serum creatinine levels increased from 115 to 208-mu-mol/l in the 1st postoperative wk. There were no serious side-effects during the first course of OKT3. In the 10 patients who received a second course of OKT3 side-effects were badly tolerated, although not hemodynamically significant or life-threatening. When the freedom from rejection in the OKT3 group was compared to the results in our first 32 cardiac recipients who also received cyclosporine and low-dose steroids there appeared to be a significant (p < 0.001) delay in the occurrence of the first rejection. This delay was not significantly different in the randomized concurrent controls. This supports the need to conduct randomized trials for the comparison of immunosuppressive regimens. OKT3 facilitated patient care by preventing nephrological problems but did not reduce the incidence of cardiac allograft rejection.