Successful small-bowel/liver transplantation

Grant, David; Wall, William; Mimeault, Richard; Zhong, Robert; Ghent, Cameron N.; García, Bertha; Stiller, C. R.; Duff, John

doi:10.1016/0140-6736(90)90275-a

Cited by 416 publications

(142 citation statements)

References 16 publications

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“…25, left), empirically developed long-term immunosuppression, with which success (called graft acceptance, not tolerance) did not depend on matching and could be accomplished without GVHD -eventually extending even to the transplantation of lymphoid-rich organs such as the intestine (12,13,49,(108)(109)(110). The GVHD resistance now can be explained by the mutual engagement and interaction of migratory cells from the allograft with the immunocytes of the recipient (a two-way MLR) (Fig.…”

Section: Two-waymlrmentioning

confidence: 99%

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

1993

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Section: Two-waymlrmentioning

confidence: 99%

Cell migration and chimerism after whole-organ transplantation: The basis of graft acceptance

1993

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“…The first successful complete small-intestine transplant in man 1 was accomplished with continuous intravenous infusion of cyclosporin. The patient briefly had donor lymphocytes in peripheral blood during the early postoperative phase and at the same time had symptoms of graft-versushost disease (GVHD).…”

mentioning

confidence: 99%

Replacement of donor lymphoid tissue in small-bowel transplants

et al. 1991

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The presence of recipient lymphocytes in grafts is thought to equate with rejection. Thus, we wished to follow the fate of lymphocytes after transplant of the small bowel. Three complete small-bowel transplants, two with the liver from the same donor also transplanted, were done successfully. Patients were immunosuppressed with FK 506. 5 to 11% of lymphocytes in the recipients' peripheral blood were of donor origin during the early postoperative period when there were no clinical signs of graftversus-host disease. However, donor cells were no longer detectable after 12 to 54 days. Serial biopsy specimens of the grafted small bowel showed progressive replacement of lymphocytes in the lamina propria by those of the recipient's HLA phenotype. Lymphoid repopulation was complete after 10 to 12 weeks but the epithelial cells of the intestine remained those of the donor. The patients are on enteral alimentation after 5, 6, and 8 months with histopathologically normal or nearly normal intestines. Re-examination of assumptions about the rejection of intestinal grafts and strategies for its prevention are required following these observations.Little is known about the fate and function of lymphocytes in intestinal grafts, partly because long-term survival after transplant of the small intestine has been difficult to achieve. The first successful complete small-intestine transplant in man 1 was accomplished with continuous intravenous infusion of cyclosporin. The patient briefly had donor lymphocytes in peripheral blood during the early postoperative phase and at the same time had symptoms of graft-versushost disease (GVHD). We have followed the fate of host and donor lymphocytes in three patients treated with FK 506-one after small-bowel transplant and two after combined liverintestine grafting.Patient 1 lost the entire small bowel and most of the colon 5 months before transplant after a gun shot wound of the superior mesenteric artery; liver function was normal. Patients 2 and 3 had had total small-bowel resection several years earlier because of necrotising enterocolitis and thrombosis of the superior mesenteric artery, respectively, and both had liver failure following parenteral hyperalimentation. All grafts received arterial blood from the aorta, and intestinal venous outflow was through the liver of patient 1 or through the liver grafts of patients 2 and 3. FK 506 for immunosuppression was given intravenously at first (0·1 mg/kg per day) and later enterally (0·3 mg/kg per day in divided doses). Maintenance doses of FK 506 were lower. Prednisolone was given initially and later stopped (patients 2 and 3) or reduced (patient 1). Patients were maintained on intravenous nutrition for at least 2 months before starting jejunostomy and, ultimately, oral feeding. continuity restored, and patient 3 is still being fed through a nasogastric tube with its tip advanced into the graft jejunum.Peripheral blood lymphocytes were isolated with 'Ficoll-Hypaque' (Pharmacia LKB) and stored in liquid nitrogen until tested. Lymphoc...

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“…Evidence supporting chimerism was found in retrospective studies of long-term survivors of kidney allografts (30 years post-transplantation), liver allografts (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) years post-transplantation) and recipients of thoracic organs. 42 ,64 The identity of donor and recipient cells was established after special staining procedures (immunostaining or sex identification after fluorescence in situ hybridization [FISH]), and polymerase chain reaction [DNA fingerprinting]).…”

Section: Chimerism and The Induction Of Graft Acceptancementioning

confidence: 97%