FK506 (TACROLIMUS) COMPARED WITH CYCLOSPORINE FOR PRIMARY IMMUNOSUPPRESSION AFTER PEDIATRIC LIVER-TRANSPLANTATION - RESULTS FROM THE US MULTICENTER TRIAL

We report on the efficacy and safety of FK506 (tacrolimus) compared wi th a cyclosporine (CsA)-based immunosuppressive regimen after 1 year o f treatment in pediatric liver allograft recipients (< 12 years) parti cipating in a multicenter U.S. randomized trial, Patients received eit her FK506 or CsA as primary immunosuppression following a first ABO-co mpatible liver transplant, Intravenous FK506 was initiated at 0.1 mg/k g per day, followed by oral FK506 beginning at 0.3 mg/kg per day, The dose was adjusted to maintain plasma trough levels of 0.5-2.0 ng/ml. T he CsA group was treated according to each center's usual protocol, Bo th groups received the same initial doses of corticosteroids, Ah rejec tion episodes were biopsy-proven and a standardized algorithm was adop ted for the treatment of rejection, Thirty patients were randomized to the FK506 group and 20 to the CsA group, After twelve months of follo w-up 20 patients remained in the FK506 group and 13 in the CsA group, Patient survivals were 80% and graft survival 70% in the FK506 group c ompared with 81% and 71% respectively, in the CsA group, 48% of the FK 506 group remained rejection-free compared with 21% of the CsA group, and 79% of FK506-treated patients did not require OKT3 compared with 6 8% of CsA treated patients, The cumulative corticosteroid dose was les s at each time point throughout the first year in the FK506 group, The incidence of serious and minor infections was similar in both groups, Nephrotoxicity, neurotoxicity, and gastrointestinal disturbances were the major toxicities reported, Differences did not reach statistical significance between the two groups although major neurologic events, diarrhea and dyspepsia were more often reported in the FK506 group. Th ere was no difference in mean serum creatinine at 12 months between th e two groups. There was a tendency toward lower mean serum cholesterol in the FK506 group. There was no hirsuitism in the FK506 group compar ed with a 30% incidence in the CsA group, In conclusion, compared with CsA, there is a trend toward less rejection in FK506-treated pediatri c allograft recipients, while both drugs have a similar spectrum of si de effects.