Conversion of liver allograft recipients from cyclosporine to FK 506-based immunosuppression: benefits and pitfalls.

C YCLOSPORINE (CyA) has been a major advance in the armamentarium of immunosuppressive agents used in clinical transplantation. The use of Cy A and steroids has increased patient and graft survival in human transplantation. 1 ,2 Rejection continues to be the most common cause of retransplantation, and death is often a sequela of treatment of rejection. A number of adverse effects of CyA have been well defined; these include nephrotoxicity, hypertension, neurotoxicity, hirsuitism, and a number of less well-defined side effects. It has been suggested that this spectrum of side effects are related to a common pathway involving the cyclophyllin receptor. 3 Alterations in clinical immunosuppression to prevent or reverse these and other side effects have included (1) reduction of CyA dose or (2) addition of azathioprine, antilymphocyte antibodies, or other agents with concomi-tant reductions in the CyA dose. These methodologies have their inherent dangers: increased susceptibility to rejection, and increased susceptibility to infection, respectively. FK 506 is a potent and novel immunosuppressive agent. report on the use of FK 506 for conversion of patients with Cy A failure to FK 506 was given. This report included the plan to administer FK 506 to 40 patients who were rejecting their liver grafts in spite of conventional immunosuppression. 4 The initial protocol was to combine low doses of FK 506 with CyA, which was attempted in the early experience; however, this combination was accompanied by a number of adverse reactions. Eventually, a simple switch (clean conversion) was made from CyA to FK 506. The following is a detailed account of the first 246 liver transplant recipients converted from CyA, steroids, and/or azathioprine to FK 506 with or without low-dose steroids. The results are analyzed by indications for entrance into the protocol. A), with the approval of the respective institutional review boards. Informed consent was obtained from patients or their appointed guardians. A minimum follow-up period of 2 months was obtained on all patients. The median follow-up period was 240 days. Two hundred forty-six patients were entered in the study. During this period, 15 other patients were converted to FK 506 from CyA at the time of retransplantation, and these results have been reported elsewhere. s Of the 246 patients converted to FK 506, 27 patients received their liver allografts at centers other than the University of Pittsburgh, but were subsequently accepted for FK 506 therapy. Most of the 246 patients were …