FK506 conversion therapy in pediatric liver transplantation.
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.
Egawa
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Department of Transplantation, California Pacific Medical Center, San Francisco 94115.
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D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D004341:Drug Evaluation; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology* / Q000706:statistics & numerical data; D008297:Male; D011184:Postoperative Period; D011446:Prospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*
D016572:Cyclosporine; D016559:Tacrolimus