THE EVOLUTION OF IMMUNOSUPPRESSION WITH FK506 IN PEDIATRIC LIVING-RELATED LIVER TRANSPLANTATION1

The effects of three FK506 induction regimens on pediatric living-related liver transplantation (LRLT) were studied retrospectively in terms of patient survival and adverse side effects. The patients consisted of 120 children, ranging from 3 to 210 months of age, who underwent a total of 122 LRLTs with a minimum follow-up of 6 months. Immunosuppression consisted of FK506 and low-dose steroids. FK506 was given in 3 ways: (1) high-dose intravenous (i.v.) induction, with FK506 begun at a dose of 0.15 mg/kg/day for the first 16 patients; (2) low-dose i.v. induction, with FK506 begun at a dose of 0.06 mg/kg/day for the next 45 patients; and (3) per os (p.o.) induction, with FK506 begun orally from the day prior to LRLT and continued postoperatively. Whole-blood trough levels of FK506 were monitored daily. Trough levels in the high induction group were often as high as 100 ng/ml compared with the level of 20 ng/ml in the p.o. induction group. Patient survivals were 75%, 89%, and 80% in the high-i.v. vs. low-i.v. vs. p.o. groups. The incidences of acute rejection were 12.5%, 22.2%, and 26.4%, and the incidences of viral infection were 56%, 38%, and 11% in the respective groups. Major adverse effects occurred with higher frequency in the high-i.v. induction group. Oral FK506 induction therapy at a dose of 0.15 mg/kg/day starting from the day before LRLT was safer and associated with a lower incidence of viral infection than therapy with i.v. FK506.