Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts: Efficacy toxicity and dose regimen in 23 children

Raymond Reding, Pierre E. Wallemacq, Monique E. Lamy, Jacques Rahier, Christine Sempoux, Benoit Debande, Jacques Jamart, Andrew Barker, Etienne Sokal, Jean De Ville De Goyet, Didier Moulin, Stéphane Clement De Clety, Jean Bernard Otte

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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 FK506 therapy had to be definitively withdrawn in 6 cases (fatal infections: n=4; persistent tremor: n=1; reason unrelated to FK506: n=l). 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 EpsteinBarr 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 overimmunosuppressed population experienced major adverse events and LPS under FK506 therapy, respectively.

Original languageEnglish
Pages (from-to)93-100
Number of pages8
JournalTransplantation
Volume57
Issue number1
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Transplantation
  • Immunology

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    Reding, R., Wallemacq, P. E., Lamy, M. E., Rahier, J., Sempoux, C., Debande, B., Jamart, J., Barker, A., Sokal, E., De Ville De Goyet, J., Moulin, D., De Clety, S. C., & Otte, J. B. (1994). Conversion from cyclosporine to FK506 for salvage of immunocompromised pediatric liver allografts: Efficacy toxicity and dose regimen in 23 children. Transplantation, 57(1), 93-100.