Stepwise minimization of the immunosuppressive therapy in pediatric liver transplantation. A conceptual approach towards operational tolerance.
The evolution of immunosuppression in pediatric liver transplantation has been characterized by a steady reduction of the immunosuppressive load, including removal of anti-lymphocyte antibodies, with the aim to reduce the incidence of EBV-related post-transplant lymphoproliferative disorders. Acute rejection rates were studied retrospectively over two decades of pediatric liver transplantation, according to the successive immunoprophylactic regimens. 318 primary pediatric liver transplant recipients, included between 1984 and 2004 in successive prospective trials, were analyzed, with respect to the impact of the immunosuppressive protocol on acute rejection occurrence. A progressive decrease of rejection incidences was observed, which corresponded to reduced immunosuppressive load and to transplant eras. Such trend might be related to changing approaches towards acute rejection histology and therapy by transplant clinicians, but also to the stepwise minimization of immunosuppressive protocols, putatively enhancing graft acceptance. We hypothesize that the recent population of liver transplant recipients with low immunosuppression might be more suitable for progressive immunosuppression withdrawal trial, with the aim to reach ultimately operational tolerance.
Reding
Raymond
R
Pediatric Liver Transplant Program, Saint-Luc University Clinics, Université catholique de Louvain, Brussels, Belgium. reding@chex.ucl.ac.be
Gras
Jérémie
J
Bourdeaux
Christophe
C
Wieers
Grégoire
G
Truong
Quang Dinh
QD
Latinne
Dominique
D
Sokal
Etienne
E
Janssen
Magda
M
Lerut
Jan
J
Otte
Jean-Bernard
JB
de Ville de Goyet
Jean
J
D000293:Adolescent; D000961:Antilymphocyte Serum / Q000187:drug effects / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007223:Infant; D016031:Liver Transplantation / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D015337:Multicenter Studies as Topic; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D013601:T-Lymphocytes / Q000276:immunology; D016559:Tacrolimus / Q000008:administration & dosage; D016896:Treatment Outcome
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D016559:Tacrolimus