Transplantation 1994 Apr 27;57(8):1169-73

FK506 conversion therapy in pediatric liver transplantation

Egawa H, Esquivel CO, So SK, Cox K, Concepcion W, Lawrence L
Department of Transplantation, California Pacific Medical Center, San Francisco
94115

Abstract

The safety and efficacy of conversion to FK506 after failing immunosuppression
with cyclosporine was prospectively evaluated in 31 pediatric liver transplant
recipients between April 1991 and March 1993. The patients, who ranged in age
from 40 days to 14 years, accounted for 28 primary transplantations and 3
retransplantations. The initial immunosuppression regimen consisted of
cyclosporine in combination with prednisone. The indications for conversion were
acute or chronic rejection refractory 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 growth retardation (1 patient). After an average follow-up of 10 months
(range, 2 to 25 months), 27 (87%) of the patients are alive and have functioning
grafts. Of the 13 patients who were converted for refractory rejection, 9 are
alive. Six of these 9 patients experienced a complete biochemical reversal of
the rejection process within 3 months of conversion; 2 had a partial response to
conversion, and 1 patient failed but 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 functioning grafts. Of the 8 patients who developed hypertension on
cyclosporine and prednisone, 6 experienced a resolution of this problem within 3
months of conversion. Three of the 18 children who underwent rescue therapy for
reasons other than refractory rejection experienced rejection episodes after
conversion to FK506. Two of these 3 children achieved resolution with either
steroid therapy or an increased dosage of FK506, while the third child developed
chronic rejection. The side effects 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
therapy for pediatric liver transplant recipients who have failed
immunosuppression with cyclosporine. Longer follow-up is needed to assess the
effect of FK506 on growth