EXPERIENCE OF FK506 IMMUNE SUPPRESSION IN PEDIATRIC HEART-TRANSPLANTATION - A STUDY OF LONG-TERM ADVERSE-EFFECTS

Background: Immunosuppression with FK506 for pediatric heart transplan tation has been used in this institution since 1989. This study report s the unique toxicity of this macrolide agent in these heart transplan t recipients. Methods: Between October 1989 and August 1994, 49 patien ts were managed with FK506, which was the initial primary agent in 38 patients. The remaining 11 were switched from cyclosporine A because o f persistent rejection or side effects from the cyclosporine A or pred nisone. Data were obtained retrospectively from medical records. Resul ts: Mean duration of follow-up was 29 months (median 37 months, range 3 to 96 months). Twenty-nine patients (59%) were receiving FK506 alone ; 20 patients (41%) were receiving additional treatment with azathiopr ine, prednisone, or methotrexate. There were seven deaths. Twenty pati ents (41%) had elevated creatinine levels between 1 to 2 mg/dl. Five p atients (11%) had levels greater than 2 mg/dl. Two patients with preex isting renal dysfunction while receiving cyclosporine A had chronic re nal failure 32 and 36 months after switching to FK506 and required kid ney transplantation. Hyperkalemia was a persistent finding in 26 patie nts. Of eight patients with hypertension, four had preexisting disease while receiving cyclosporine A; two had impaired renal function, and two were receiving prednisone. Severe anemia developed in eight patien ts (16%), two of whom had parvovirus. Moderate anemia developed in 21 patients (43%). Eosinophilia occurred in 19 patients; 11 of 19 patient s (58%) had allergic symptoms. There was one case of diabetes mellitus . There were 12 significant infections with four infection-related dea ths. Lymphoproliferative disease was noted in three patients, two of w hom survived. Gastrointestinal symptoms, including chronic diarrhea, r ecurrent abdominal pain, and reflux esophagitis were present in 10 pat ients. Conclusions: In our experience, anemia, renal toxicity, hyperka lemia, chronic diarrhea, and allergies were the most common adverse ef fects of FK506. Unlike cyclosporine A, hypertension, gingival hyperpla sia, coarsening of facial features, and hirsutism were not seen.