Clinical intestinal transplantation: New perspectives and immunologic considerations

Kareem Abu-Elmagd, Jorge Reyes, Satoru Todo, Abdul Rao, Randall Lee, William Irish, Hiro Furukawa, Javier Bueno, John McMichael, Ahmed T. Fawzy, Noriko Murase, Jake Demetris, Jorge Rakela, John J. Fung, Thomas E. Starzl

Research output: Contribution to journalArticle

221 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)512-527
Number of pages16
JournalJournal of the American College of Surgeons
Volume186
Issue number5
DOIs
StatePublished - 1998
Externally publishedYes

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Intestines
Transplantation
Transplants
Graft Rejection
Tacrolimus
Immunosuppression
Allografts
Bone Marrow
Tissue Donors
Chimerism
Liver
B-Cell Lymphoma
Graft vs Host Disease
Bone Marrow Cells
Leukocytes
Rehabilitation
Morbidity
Safety
Survival
Mortality

ASJC Scopus subject areas

  • Surgery

Cite this

Clinical intestinal transplantation : New perspectives and immunologic considerations. / Abu-Elmagd, Kareem; Reyes, Jorge; Todo, Satoru; Rao, Abdul; Lee, Randall; Irish, William; Furukawa, Hiro; Bueno, Javier; McMichael, John; Fawzy, Ahmed T.; Murase, Noriko; Demetris, Jake; Rakela, Jorge; Fung, John J.; Starzl, Thomas E.

In: Journal of the American College of Surgeons, Vol. 186, No. 5, 1998, p. 512-527.

Research output: Contribution to journalArticle

Abu-Elmagd, K, Reyes, J, Todo, S, Rao, A, Lee, R, Irish, W, Furukawa, H, Bueno, J, McMichael, J, Fawzy, AT, Murase, N, Demetris, J, Rakela, J, Fung, JJ & Starzl, TE 1998, 'Clinical intestinal transplantation: New perspectives and immunologic considerations', Journal of the American College of Surgeons, vol. 186, no. 5, pp. 512-527. https://doi.org/10.1016/S1072-7515(98)00083-0
Abu-Elmagd, Kareem ; Reyes, Jorge ; Todo, Satoru ; Rao, Abdul ; Lee, Randall ; Irish, William ; Furukawa, Hiro ; Bueno, Javier ; McMichael, John ; Fawzy, Ahmed T. ; Murase, Noriko ; Demetris, Jake ; Rakela, Jorge ; Fung, John J. ; Starzl, Thomas E. / Clinical intestinal transplantation : New perspectives and immunologic considerations. In: Journal of the American College of Surgeons. 1998 ; Vol. 186, No. 5. pp. 512-527.
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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.",
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AU - Abu-Elmagd, Kareem

AU - Reyes, Jorge

AU - Todo, Satoru

AU - Rao, Abdul

AU - Lee, Randall

AU - Irish, William

AU - Furukawa, Hiro

AU - Bueno, Javier

AU - McMichael, John

AU - Fawzy, Ahmed T.

AU - Murase, Noriko

AU - Demetris, Jake

AU - Rakela, Jorge

AU - Fung, John J.

AU - Starzl, Thomas E.

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N2 - 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.

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