The effect of timing on outcome using tacrolimus (T) rescue for liver transplant (LT) recipients with rejection

T is approved in the U.S. for primary immunosuppression in LT recipients. Heretofore, the use of T for treatment of allografl rejection (AR) has been limited to patients failing OKT3 therapy. The U.S. Multicenter FK 506 Trial showed a decreased need for OKT3 to control AR in patients receiving T. We theorized that use of T rescue at a point prior to the use of OKT3 might decrease the need for OKT3 and, thus, lead to less patient morbidity and decreased cost of LT. METHODS: Between 8/94-8/95, 97 patients underwent first liver transplants. 79 patients received cyclosporine (C)-based and 14 T-based primary immunosuppression (4 received neither). Patient survival was 93% and the corresponding graft survival was 91%. Recipients initially receiving a C-based regimen and who received T as treatment for AR prior to the use of OKT3 were compared to 2 control groups: patients immunosuppressed with C-based regimen who received OKT3 prior to T and patients who received T as primary therapy. RESULTS: 63% of patients experienced at least 1 episode of AR. 61% of T-based and 64% of C-based patients. 26% of patients were treated for AR with steroids alone. 16% of C-based and 21% of T-based patients required OKT3. 43% of C-treated patients were converted to T because of AR. 5 patients (15%) were converted to T concomitant with the first episode of AR. 5 patients after completion of 1 course of anti-rejection therapy. 18 patients (64%) were converted at the onset of a second episode of rejection, either alone or in combination with a second course of corticosteroids. 2 patients were converted after a third episode of allograft rejection. 13 patients received OKT3 as treatment of rejection prior to conversion to tacrolimus. Of the 24 patient who were converted to tacrolimus before the use of OKT3, only 1/24 (4%) subsequently required OKT3 to control AR. 16 of the 97 patients (17%) received OKT3 therapy for allograft rejection. This compares with the use of OKT3 in 29% of all patients transplanted in the preceding year and 11% in patients who received tacrolimus as primary therapy. CONCLUSIONS: The need for OKT3 treatment of AR appears to decrease with the use of T rescue at a point prior to where OKT3 has been traditionally used. This should lead to a decrease in patient morbidity and costs of liver transplantation. Whether T-based rescue is superior to T-based primary immunosuppression remains to be determined.