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Reduction of lymphoid tissue by splenectomy and/or thymectomy has been used as a part of immunosuppression in organ transplantation (4). More recently Walker (7), Johnson (2), Franksson (1) and Starzl (5,6) and their associates have shown that chronic depletion of lymphocytes by thoracic duct drainage decreases the incidence of rejection and hence increases renal graft survival. Mechanical removal of lymphocytes from circulation peripheral blood should theoretically achieve the same or similar effect on the immunity as thoracic duct drainage. Since September, 1979, five organ transplant recipients have received multiple lymphocytapheresis by IBM 2997 Blood Cell Separator as a mechanical pretransplant immunosuppression. The changes in cellular and humoral immunity and the clinical outcome are presented in this report.

From March 1980 to July 1987, 1000 patients with various end-stage liver diseases received orthotopic liver transplants. Of the 1000 patients, three hundred two had definite histories of bleeding from esophageal varices before transplantation. There were 287 patients with nonalcoholic liver diseases and 15 patients with alcoholic cirrhosis. All patients had very poor liver function, which was the main indication for liver transplantation. One- through 5-year actuarial survival rates of the 302 patients were 79%, 74%, 71%, and 71%, respectively. These survival rates are far better than those obtained with other available modes of treatment for bleeding varices when liver disease is advanced. Long-term sclerotherapy is the treatment of primary choice for bleeding varices. Patients in whom sclerotherapy fails should be considered for liver transplantation unless clear contraindications exist.

Ten patients received liver transplants for unresectable epithelioid hemangioendothelioma (EHE). At the time of transplantation, four patients had microscopic metastases to the hilar lymph nodes, and one of the four also had metastases to a rib. The fifth patient had metastases to the lung, pleura, and diaphragm. The remaining five patients were believed to be free of metastatic disease. Two of these five patients died of metastatic disease at 3 and 16 months, respectively, after transplantation. Interestingly, all five patients with metastatic involvement are currently alive 40.6 ± 22 months (mean ± standard error of mean [SEM]) after transplantation, although one of these patients currently has metastatic disease to the lungs and mediastinum. Thus, the projected 5‐year actuarial survival rate is 76%, with two patients at risk after the third year. In conclusion, liver transplantation is a reasonable procedure for bulky, otherwise unresectable, EHE even in the presence of metastatic disease. Copyright © 1988 American Cancer Society

An analysis of more than 500 liver transplants has demonstrated that HLA compatibility is associated with diminished allograft survival. Liver transplants with zero mismatches for class I and/or class II HLA antigens have shown significantly lower acturial survival rates than transplants with one or more mismatches for these loci. In a group of 199 failed liver allografts from patients undergoing retransplantation, a higher incidence of failure due to rejection correlated with a lower degree of HLA compatibility especially for HLA-DR. In contrast, the incidence of liver transplant failures due to primary nonfunction was relatively higher with HLA-DR compatible transplants. Considering the role of HLA as a restriction element in cellular interactions during the immune response, these findings suggest that HLA compatibility may have a dualistic effect on liver transplant outcome. On one hand, HLA compatibility reduced transplant rejection - and on the other hand, it may enhance other immunological mechanisms leading to allograft dysfunction, particularly in patients at risk of developing recurrent autoimmune diseases or infection.

Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt should not be a contraindication for hepatic transplantation.

Eighteen patients were treated with primary cadaveric renal transplantation using cyclosporin A therapy, and four more patients underwent cadaveric retransplantation. Eleven of the 22 recipients were conditioned with lymphoid depletion before transplantation, using thoracic duct drainage or lymphapheresis for two to eight and one-half weeks. cyclosporin A was begun a few hours before grafting. The other 11 patients were pretreated wtih cyclosporin A for from one day to 18 days. After transplantation, the majority of patients in both subgroups of 11 had rejection develop, but in most, the immunologic process was readily controlled with relatively small dosages of prednisone. After follow-up periods of two to four and one-half months, one patient has died of the complications of a coronary artery reconstruction that was not related to the transplantation. Another graft was lost from rejection, and a third organ was removed because of ureteral necrosis. Nineteen of the original 22 cadaveric kidneys are functioning, including 17 of the 18 kidneys given to patients who were undergoing transplantation for the first time. The only loss in the latter group of 18 patients was in the patient who died after an open heart operation. Results of these studies have shown that cyclosporin A is a superior and safe immunosuppressive drug but that, for optimal use in cadaveric transplantation, it usually should not be given alone. Steroid therapy greatly amplified the value of cyclosporin A. Unless major delayed morbidity develops which is not obvious so far, this drug combination should permit revolutionary advances ion the transplantation of all organs. Other adjunct to the cyclosporin A-steroid combination, including lymphoid depletion techniques, will require further investigation.

In this report, we address combined liver-kidney transplantation, with particular attention to the apparent phenomenon of protection of kidney allografts to antibody mediated destruction by liver allografts. Four patients were found to have positive crossmatch before the liver phase of the combined transplant (pre-OT/KT samples). These positive crossmatches were due entirely to anti-HLA class I antibodies, as demonstrated by their removal by immunoabsorption on pololed platelets. In three of these patients, post-OT/pre-KT samples showed a conversion to a negative crossmatch (in the fourth patient this was not done). A kidney allograft, harveted from the same donor, was then placed into the recipient, and in patients no. 3, 7, and 12, good initial function was noted. In one of these patients was there evidence of hyperacute rejection. Post-OT/KT samples were collected in patients no. 3, 7, and 8, and then analyzed for the reappearance of donor specific lymphocytotoxic antibodies in the posttransplant period (data on patient no. 12 was not available at time of preparation). Lymphocytotoxic antibodies with donor specificity could not be detected in any of the samples during the first week posttransplant. The decrease in %PRA and conversion of a positive to negative crossmatch following liver transplantation was correlated to the HLA specificty of the antibody found in the pretransplant serum and the HLA type of the tranplanted organs. In the two instances where an HLA specificity could be determined by panel analysis, transplantation with donor organs bearing these HLA specificities led to a specific disppearance of these antibodies during the postransplant phase.