Original Scientific Articles
Clinical Intestinal Transplantation: New Perspectives and Immunologic Considerations 1

Presented at the American College of Surgeons 83rd Annual Clinical Congress, Chicago, October 1997.
https://doi.org/10.1016/S1072-7515(98)00083-0Get rights and content

Abstract

Background: Although tacrolimus-based immunosuppression has made intestinal transplantation feasible, the risk of the requisite chronic high-dose treatment has inhibited the widespread use of these procedures. We have examined our 1990–1997 experience to determine whether immunomodulatory strategies to improve outlook could be added to drug treatment.

Study Design: Ninety-eight consecutive patients (59 children, 39 adults) with a panoply of indications received 104 allografts under tacrolimus-based immunosuppression: intestine only (n = 37); liver and intestine (n = 50); or multivisceral (n = 17). Of the last 42 patients, 20 received unmodified adjunct donor bone marrow cells; the other 22 were contemporaneous control patients.

Results: With a mean followup of 32 ± 26 months (range, 1–86 months), 12 recipients (3 intestine only, 9 composite grafts) are alive with good nutrition beyond the 5-year milestone. Forty-seven (48%) of the total group survive bearing grafts that provide full (91%) or partial (9%) nutrition. Actuarial patient survival at 1 and 5 years (72% and 48%, respectively) was similar with isolated intestinal and composite graft recipients, but the loss rate of grafts from rejection was highest with intestine alone. The best results were in patients between 2 and 18 years of age (68% at 5 years). Adjunct bone marrow did not significantly affect the incidence of graft rejection, B-cell lymphoma, or the rate or severity of graft-versus-host disease.

Conclusions: These results demonstrate that longterm rehabilitation similar to that with the other kinds of organ allografts is achievable with all three kinds of intestinal transplant procedures, that the morbidity and mortality is still too high for their widespread application, and that the liver is significantly but marginally protective of concomitantly engrafted intestine. Although none of the endpoints were markedly altered by donor leukocyte augmentation (and chimerism) with bone marrow, establishment of the safety of this adjunct procedure opens the way to further immune modulation strategies that can be added to the augmentation protocol.

Section snippets

Recipient

Case accrual was between May 2, 1990 and August 11, 1997, during which 98 patients received 104 intestinal grafts: 35 alone, 48 with a liver, and 15 as part of a multivisceral graft. Of the 6 retransplantations, 2 were isolated intestine and 4 were liver-intestine or multivisceral. Children (0.5–16.8 years) outnumbered adults (18–58 years), and gender distribution was nearly equal. Other demographic and clinical features are summarized in Table 1. The causes of intestinal failure are listed in

Overall

Current survivors who are still bearing their grafts (n = 47) have been followed up for 32 ± 26 months (range, 1–86 months); 2 are successful retransplant recipients (one isolated intestine, and one combined liver-intestine). Fifteen recipients survived more than 5 years. Kaplan-Meier survival rate is 72% at 1 year and 48% at 5 years (Fig. 2). Most of the deaths occurred during the first 30 postoperative months.

The survival rate was similar among the three different types of transplantation (p

Discussion

Empirical progress in organ transplantation depended for 30 years on a search for more potent baseline immunosuppressants, without understanding the basis for the prototypic immunologic confrontation (rejection) and involution (“graft acceptance”) that was first observed in kidney recipients treated with azathioprine and prednisone.[36]The advent of cyclosporine elevated the expectations with transplantation of most organs to the level of patient service, but the resulting revolution largely

Acknowledgements

Acknowledgment:

We would like to thank Dolly Martin, Lynn Ostrowski, Anita Krajack, Mauricio Geraldo, MD, and Scott Miller for their great help in data collection.

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      Over the years several strategies have been proposed with intent of attenuating the intestinal allograft immunogenicity and shifting it to a tolerogenic status. The concept of reducing the T-cell load in the recipient to minimize rejection was first proposed by the Pittsburgh group in 1995 [33], with the introduction of lymphocyte depleting therapy with Cyclophosphamide induction immunosuppression, which was later replaced by anti-IL-2R antibodies (Ab) [34] (daclixumab and basiliximab). This led to a significant reduction of the early post-transplant rejection (10%–20%).

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    This study was supported in part by Project Grant No. DK 29661 from the National Institutes of Health, Bethesda, MD.

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