FK506 CONVERSION THERAPY IN PEDIATRIC LIVER-TRANSPLANTATION

The safety and efficacy of conversion to FH506 after failing immunosup pression with cyclosporine was prospectively evaluated in 31 pediatric liver transplant recipients between April 1991 and March 1993. The pa tients, who ranged in age from 40 days to 14 years, accounted for 28 p rimary transplantations and 3 retransplantations. The initial immunosu ppression regimen consisted oc cyclosporine in combination with predni sone. The indications for conversion were acute or chronic rejection r efractory to OKT3, Minnesota antilymphocyte globulin, or steroids (13 patients); hypertension (8 patients); inability to reach a therapeutic level of cyclosporine (6 patients); hirsutism (3 patients); and growt h retardation (1 patient). After an average follow-up of 10 months (ra nge, 2 to 25 months), 27 (87%) of the patients are alive and have func tioning grafts. Of the 13 patients who were converted for refractory r ejection, 9 are alive. Six of these 9 patients experienced a complete biochemical reversal of the rejection process within 3 months of conve rsion; 2 had a partial response to conversion, and 1 patient failed bu t underwent successful retransplantation. Three of the 4 patients who died did so without showing any improvement. The remaining 18 patients who were converted for various other reasons are alive and have funct ioning grafts. Of the 8 patients who developed hypertension on cyclosp orine and prednisone, 6 experienced a resolution of this problem withi n 3 months of conversion. Three of the 18 children who underwent rescu e therapy for reasons other than refractory rejection experienced reje ction episodes after conversion to FK506. Two of these 3 children achi eved resolution with either steroid therapy or an increased dosage of FK506, while the third child developed chronic rejection. The side eff ects of FK506 were generally minor and resolved by lowering the dose. Lymphoproliferative disease developed in 2 patients (6%). The present study suggests that FK506 is a relatively safe and effective rescue th erapy for pediatric liver transplant recipients who have failed immuno suppression with cyclosporine. Longer follow-up is needed to assess th e effect of FK506 on growth.