Management of acute steroid-resistant rejection after liver transplantation

Prior to the FK506 era, OKT3 was primarily used for treatment of steroid-resistant rejection. Initially FK506 has been used as a last treatment of refractory acute or chronic rejection. We provide strong evidence that the use of FK506 is more successful if rescue therapy is performed early instead of using it as the last resort. Between September 1988 and March 1995 a total of 600 liver transplantations were performed in 550 patients. Of these 550 patients, 426 received primarily cyclosporine A (CsA)-based immunosuppression. Of the 426 CsA patients, 70 (16.4%) required either FK506 (51.4%), or OKT3 rescue therapy (27.1%), or a combination of the two drugs (21.5%). The latter group of patients received first OKT3 and then FK506 rescue when OKT3 therapy failed. Treatment was initiated simultaneously (within 1 week) in 11 patients, and 4 patients received FK506 rescue later during the course of rejection. The highest success rates (88.9%) were observed in patients given FK506 rescue therapy. Retransplantation was necessary more often in patients receiving OKT3 than in those with FK506 rescue therapy (15.8% versus 5.5%, respectively). Retransplantation and death due to chronic rejection increased with the need for additional FK506 rescue therapy after OKT3 failure. This increase was most pronounced in patients receiving FK506 during the late course of rejection, reaching a failure rate of 75.0% (50. 0% of deaths were due to chronic rejection). The lowest incidence of cytomegalovirus infection and of infectious, neurologic, and renal complications was observed in the FK506 rescue group. We conclude that early FK506 rescue therapy may be the treatment of choice for acute steroid-resistant rejection.