Clinical intestinal transplantation: a decade of experience at a single center

Abstract

Objective: To assess the long-term efficacy of intestinal transplantation under tacrolimus-based immunosuppression and the therapeutic benefit of newly developed adjunct immunosuppressants and management strategies.

Summary background data: With the advent of tacrolimus in 1990, transplantation of the intestine began to emerge as therapy for intestinal failure. However, a high risk of rejection, with the consequent need for acute and chronic high-dose immunosuppression, has inhibited its widespread application.

Methods: During an 11-year period, divided into two segments by a 1-year moratorium in 1994, 155 patients received 165 intestinal allografts under immunosuppression based on tacrolimus and prednisone: 65 intestine alone, 75 liver and intestine, and 25 multivisceral. For the transplantations since the moratorium (n = 99), an adjunct immunosuppressant (cyclophosphamide or daclizumab) was used for 74 transplantations, adjunct donor bone marrow was given in 39, and the intestine of 11 allografts was irradiated with a single dose of 750 cGy.

Results: The actuarial survival rate for the total population was 75% at 1 year, 54% at 5 years, and 42% at 10 years. Recipients of liver plus intestine had the best long-term prognosis and the lowest risk of graft loss from rejection (P =.001). Since 1994, survival rates have improved. Techniques for early detection of Epstein-Barr and cytomegaloviral infections, bone marrow augmentation, the adjunct use of the interleukin-2 antagonist daclizumab, and most recently allograft irradiation may have contributed to the better results.

Conclusion: The survival rates after intestinal transplantation have cumulatively improved during the past decade. With the management strategies currently under evaluation, intestinal transplant procedures have the potential to become the standard of care for patients with end-stage intestinal failure.

Figure 1. The yearly number and kinds of intestinal transplant procedures performed since 1990. Note the 1994 moratorium.

Figure 10. Cumulative risk of graft loss from rejection in the intestine-only and composite visceral grafts that contained liver.

Figure 11. Cumulative risk of posttransplant lymphoproliferative disease (PTLD) according to era (A) and bone marrow augmentation (B).

Figure 12. Cumulative risk of cytomegaloviral (CMV) disease among patients who were transplanted before and after the 1994 moratorium.

Figure 2. Transplantation of a modified multivisceral graft (unshaded organs) containing the pancreas and all of the hollow intraabdominal viscera in continuity from the esophagogastric junction to the terminal ileum. The native liver, spleen, pancreas, and a C loop of duodenum have been retained. The procedure was used to treat a patient with pseudoobstruction. Biliary drainage from the native liver as well as from both pancreases was accomplished with a side-to-side host-to-graft duodenal anastomosis. The insert shows preservation of the donor splenic (DSA) and left gastric (DLGA) arteries (with Carrel patch) with ligation of the donor hepatic artery (DHA) stump. Note that an interposition arterial graft was initially anastomosed to the recipient infrarenal aorta and before allograft implantation. RSA, recipient splenic artery; RSV, recipient splenic vein; RBD, recipient bile duct; RPV, recipient portal vein; DSMV, donor superior mesenteric vein; DSMA, donor superior mesenteric artery.

Figure 3. The use of a modified multivisceral graft (stomach, duodenum, pancreas, and small bowel) after abdominal visceral exenteration with preservation of the host liver and spleen (shaded organs). The portosplenic circulation is maintained intact during graft insertion and the preserved spleen protects the patient from the risk of posttransplant lymphoproliferative disease. This modified multivisceral transplantation has been used to treat recipients with massive gastrointestinal polyposis and extensive Crohn’s disease. Note the duct-to-duct biliary reconstruction. RSA, recipient splenic artery; RSV, recipient splenic vein; RBD, recipient bile duct; DSA, donor splenic artery; DLGA, donor left gastric artery; DBD, donor bile duct.

Figure 4. Tacrolimus whole blood 12-hour trough levels and tacrolimus and prednisone doses in recipients who received tacrolimus and prednisone only and those who received an adjunct induction therapy with either cyclophosphamide or daclizumab.

Figure 5. Kaplan-Meier patient and graft survival curves for the total population.

Figure 6. Kaplan-Meier survival curves of the three different types of intestinal grafts.

Figure 7. Patient (A) and graft (B) survival rates before and after the 1994 moratorium.

Figure 8. Patient (A) and graft (B) survival rates for the bone marrow-augmented and control groups.

Figure 9. Tacrolimus whole blood 12-hour trough levels and tacrolimus and prednisone doses in the patients who were transplanted before and after the 1994 moratorium.