title: Prope tolerance after pediatric liver transplantation.
abstract: pT, under mono- and infratherapeutic calcineurin inhibition, may constitute an optimal condition combining graft acceptance with low IS load and minimal IS-related toxicity. We reviewed 171 pediatric (<15.0 yr) survivors beyond one yr after LT, transplanted between April 1999 and June 2007 under tacrolimus-based regimens (median follow-up post-LT: 6.0 yr, range: 0.8-9.5 yr). Their current status regarding IS therapy was analyzed and correlated with initial immunoprophylaxis. pT was defined as tacrolimus monotherapy, with mean trough blood levels <4 ng/mL during the preceding year of follow-up, combined with normal liver function tests. The 66 children transplanted before April 2001 received a standard tacrolimus-steroid regimen. Beyond April 2001, 105 patients received steroid-free tacrolimus-basiliximab or tacrolimus-daclizumab immunoprophylaxis. In the latter group, 43 (41%) never experienced any acute rejection episode and never received steroids. In the long term, a total of 79 recipients (47%) developed pT (n = 73) or IS-free operational tolerance (n = 6), 27 of them belonging to the 43 steroid-free patients (63%). In contrast, only 52/128 (41%) children treated with steroids subsequently developed prope/operational tolerance (p = 0.012). Steroid-free tacrolimus-based IS seems to promote long-term graft acceptance under minimal/no IS. These results constitute the first evidence that minimization of IS, including steroid avoidance, might be tolerogenic in the long term after pediatric LT.
authors.affiliation: Pediatric Surgery and Transplant Unit, Saint-Luc University Clinics, Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Bourdeaux
authors.forename: Aurore
authors.initials: A
authors.lastname: Pire
authors.forename: Magda
authors.initials: M
authors.lastname: Janssen
authors.forename: Xavier
authors.initials: X
authors.lastname: Stéphenne
authors.forename: Francoise
authors.initials: F
authors.lastname: Smets
authors.forename: Etienne
authors.initials: E
authors.lastname: Sokal
authors.forename: Catherine
authors.initials: C
authors.lastname: de Magnée
authors.forename: Fabio
authors.initials: F
authors.lastname: Fusaro
authors.forename: Raymond
authors.initials: R
authors.lastname: Reding
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D000077552:Basiliximab; D002648:Child; D002675:Child, Preschool; D000077561:Daclizumab; D006084:Graft Rejection; D006085:Graft Survival; D006801:Humans; D007108:Immune Tolerance; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D016031:Liver Transplantation; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use; D013256:Steroids / Q000009:adverse effects / Q000627:therapeutic use; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D013256:Steroids; D000077552:Basiliximab; D000077561:Daclizumab; D016559:Tacrolimus