title: Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts. Efficacy, toxicity, and dose regimen in 23 children.
abstract: Twenty-three pediatric liver transplant recipients (median age 3.9 years) were converted from cyclosporine A-based immunosuppression to FK506 for uncontrollable acute rejection (AR; n = 16), chronic rejection (n = 4), or predominantly nonspecific hepatitis (n = 3). Of these, 19 had received poly- or monoclonal anti-T lymphocyte antibodies either for AR prophylaxis or therapy before FK506 conversion. Full clinical and histologic responses to FK506 therapy were observed in 11/16 cases of AR compared with 0/7 cases of non-AR indications (P = 0.006). Acute FK506 toxicity included renal dysfunction in 12/23 children (52%), neurological disorders in 7/23 (30%), and isolated hyperkalemia in 2/23 (9%), with a poor correlation with the corresponding FK506 trough plasma level. Moreover, a significant impairment of glomerular filtration rate was recorded in the 12 children who received FK506 treatment for more than 6 months (P = 0.002). FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n = 4; persistent tremor: n = 1; reason unrelated to FK506: n = 1). Five children developed a lymphoproliferative syndrome (LPS), leading to death in 3 cases despite cessation of the immunosuppressive therapy; in the other 2 patients, LPS was controlled, and the children were successfully retransplanted for chronic rejection under FK506. The occurrence of Epstein-Barr virus primary infection under FK506 therapy was found to constitute a significant risk factor for LPS (P = 0.027). In summary, full response to FK506 conversion was observed in 69% of uncontrollable AR cases; however, 74% and 22% of this probably over-immunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.
authors.affiliation: Department of Surgery, University of Louvain Medical School, Brussels, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Reding
authors.forename: P E
authors.initials: PE
authors.lastname: Wallemacq
authors.forename: M E
authors.initials: ME
authors.lastname: Lamy
authors.forename: J
authors.initials: J
authors.lastname: Rahier
authors.forename: C
authors.initials: C
authors.lastname: Sempoux
authors.forename: B
authors.initials: B
authors.lastname: Debande
authors.forename: J
authors.initials: J
authors.lastname: Jamart
authors.forename: A
authors.initials: A
authors.lastname: Barker
authors.forename: E
authors.initials: E
authors.lastname: Sokal
authors.forename: J
authors.initials: J
authors.lastname: De Ville de Goyet
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D016572:Cyclosporine; D016559:Tacrolimus