title: Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion.
abstract: Long-term results of organ transplantation are still limited by serious side effects of immunosuppressive drugs. A major issue, therefore, is to elaborate novel therapeutic protocols allowing withdrawal or minimization of immunosuppressive therapy after transplantation. We report on 3 patients prospectively enrolled in an original protocol designed to promote graft acceptance in living donor liver transplantation, using posttransplant conditioning with high doses of antithymocyte globulin followed by injection of donor-derived stem cells. In 2 patients, early immunosuppression withdrawal was possible, without subsequent graft deterioration. In these 2 cases, in vitro studies showed indices of immunological tolerance as assessed by specific hyporesponsiveness to donor alloantigens in mixed lymphocytes culture. In the third patient, acute rejection rapidly occurred after discontinuation of immunosuppression, and minimal immunosuppression has to be maintained during long-term follow-up. In this case, a clearly distinct immunoreactive profile was observed as compared to tolerant patients, as no specific modulation of the antidonor response was observed in vitro. Of note, no macrochimerism could be detected in any of the 3 patients during the follow-up. In conclusion, these clinical observations demonstrated that, despite the absence of macrochimerism, donor stem cells infusion combined with recipient conditioning may allow early immunosuppression withdrawal or minimization after liver transplantation.
authors.affiliation: Medicosurgical Department of Hepatogastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels. vdonckie@ulb.ac.be
authors.forename: Vincent
authors.initials: V
authors.lastname: Donckier
authors.forename: Roberto
authors.initials: R
authors.lastname: Troisi
authors.forename: Alain
authors.initials: A
authors.lastname: Le Moine
authors.forename: Michel
authors.initials: M
authors.lastname: Toungouz
authors.forename: Salvatore
authors.initials: S
authors.lastname: Ricciardi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colle
authors.forename: Hans
authors.initials: H
authors.lastname: Van Vlierberghe
authors.forename: Ligia
authors.initials: L
authors.lastname: Craciun
authors.forename: Myriam
authors.initials: M
authors.lastname: Libin
authors.forename: Marleen
authors.initials: M
authors.lastname: Praet
authors.forename: Lucien
authors.initials: L
authors.lastname: Noens
authors.forename: Patrick
authors.initials: P
authors.lastname: Stordeur
authors.forename: Marc
authors.initials: M
authors.lastname: Andrien
authors.forename: Micheline
authors.initials: M
authors.lastname: Lambermont
authors.forename: Michel
authors.initials: M
authors.lastname: Gelin
authors.forename: Nadine
authors.initials: N
authors.lastname: Bourgeois
authors.forename: Michael
authors.initials: M
authors.lastname: Adler
authors.forename: Bernard
authors.initials: B
authors.lastname: de Hemptinne
authors.forename: Michel
authors.initials: M
authors.lastname: Goldman
mesh_terms: D000961:Antilymphocyte Serum / Q000627:therapeutic use; D017809:Fatal Outcome; D005500:Follow-Up Studies; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007519:Isoantigens / Q000276:immunology; D016031:Liver Transplantation / Q000276:immunology*; D019520:Living Donors; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D011446:Prospective Studies
chemical_list: D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D007519:Isoantigens