Clinical intestinal transplantation: new perspectives and immunologic considerations.
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.


METHODS
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.
Abu-Elmagd
K
K
Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, PA 15213, USA.
Reyes
J
J
Todo
S
S
Rao
A
A
Lee
R
R
Irish
W
W
Furukawa
H
H
Bueno
J
J
McMichael
J
J
Fawzy
A T
AT
Murase
N
N
Demetris
J
J
Rakela
J
J
Fung
J J
JJ
Starzl
T E
TE
D000206:Actuarial Analysis; D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D005240:Feasibility Studies; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000209:etiology; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007223:Infant; D007422:Intestines / Q000637:transplantation*; D017708:Leukocyte Transfusion; D016031:Liver Transplantation; D016393:Lymphoma, B-Cell / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009747:Nutritional Physiological Phenomena; D012307:Risk Factors; D012449:Safety; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018183:Transplantation Chimera; D014181:Transplantation Immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D016559:Tacrolimus