CLINICAL IMMUNOSUPPRESSION - LIVER

C.A. Bonham¹, A. Gallo², C.O. Esquivel³, W. Concepcion⁴, S. Strober^5
1Sugery, Division Of Transplantation, Stanford University, Palo Alto/UNITED STATES OF AMERICA, ²Surgery, Division Of Transplantation, Stanford University, Palo Alto/UNITED STATES OF AMERICA, ³Surgery/transplantation, Stanford University, Stanford/CA/UNITED STATES OF AMERICA, ⁴, Stanford University, stanford/UNITED STATES OF AMERICA, ⁵Medicine, Stanford University, Stanford/UNITED STATES OF AMERICA

Body: INTRODUCTION: Previous studies in rodents have shown thatimmune tolerance to MHC-mismatched heart transplants in recipients conditioned with TLI and ATG requiresan infusion of donor bone-marrow cells and development of chimerism. In contrast, almost all Lewis rat recipients of ACI liver transplants develop tolerance after TLI and ATG without a donor cellinfusion. Based on these results, we developed a clinical protocol in which liver transplant patients were conditioned with post-transplant TLI and ATGstarting, and systematically weaned from immunosuppression.

METHODS: Patients received post-transplant TLI (10 doses of 80cGy each) starting on posttransplant days 3-5, and 5 doses of ATG daily. Patients were maintained on daily conventionaldoses of tacrolimus for 3 months, then were tapered to discontinuation at 6 months. Tapering was performed by gradual reduction of the number of days per week of tacrolimus therapy. The protocolconsidered patients with rejection episodes as failures. These patients were returned to standard immunosuppressive drug therapy.

RESULTS: At present, 9 patients have been enrolled in the protocol. Difficulty managing recurrent hepatitis C preventeddiscontinuation of immunosuppressive therapy in 5 of 6 patients. Three patients without hepatitis C were successfully weaned from immunosuppressive therapy without any episodes of rejection. Nosevere infections have been observed other than recurrence of hepatitis C.

CONCLUSION: We have applied the tolerance induction protocol of post-transplant TLI and ATG that was successful in preclinical studies to patients undergoing liver transplantation. The protocol has been well tolerated, and tapering of immunosuppressive drugs has not been associated with rejection episodes in patientswithout hepatitis C.

Disclosure: All authors have declared no conflicts of interest.