Early immunosuppression withdrawal after living donor liver transplantation and donor stem cell infusion.
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.
Donckier
Vincent
V
Medicosurgical Department of Hepatogastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Brussels. vdonckie@ulb.ac.be
Troisi
Roberto
R
Le Moine
Alain
A
Toungouz
Michel
M
Ricciardi
Salvatore
S
Colle
Isabelle
I
Van Vlierberghe
Hans
H
Craciun
Ligia
L
Libin
Myriam
M
Praet
Marleen
M
Noens
Lucien
L
Stordeur
Patrick
P
Andrien
Marc
M
Lambermont
Micheline
M
Gelin
Michel
M
Bourgeois
Nadine
N
Adler
Michael
M
de Hemptinne
Bernard
B
Goldman
Michel
M
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
D000961:Antilymphocyte Serum; D007166:Immunosuppressive Agents; D007519:Isoantigens