- Email: [email protected]
Total Lymphoid Irradiation in Renal Transplantation
TRANSPLANTATION
1157
Total Lymphoid Irradiation in Renal Transplantation
Organ Transplantation: From Laboratory to Clinic
J. A. MYBURGH, J. A. SMIT, A. M. MEYERS, J. R. BOTHA, S. BROWDE AND P. D. THOMSON, Transplantation Research Unit, Department of Surgery, and Departments of Medicine, Radiotherapy and Pediatrics, University of the Witwatersrand and the Johannesburg Hospital, Johannesburg, South Africa
R. Y. CALNE, Department of Surgery, University of Cambridge Clinical School, Cambridge, England
Brit. Med. J., 291: 1751-1754 (Dec. 21) 1985
The author reports on the evolution of organ transplantation the early work of Hume on the kidney to current problems from World J. Surg., 10: 369-380 (June) 1986 with pancreatic transplantation. A succinct history of the Total lymphoid irradiation is a uniquely powerful method of Hume-Merrill experience with renal transplantation of kidneys producing transplantation tolerance. For tolerance production taken from dead donors or "free" kidneys (those removed with total lymphoid irradiation alone in the baboon a wide field during the course of other operations) is presented. The longest of irradiation, involving subtotal bone marrow irradiation as survival was only 5½ months but little, if any, steroids were well as lymphoid irradiation, is essential. Donor bone marrow used as an immunosuppressive agent. Transplantation between injection is not necessary for tolerance production with pri- identical twins was so successful that added impetus was given marily vascularized organ grafts (hence no risk of graft versus to understanding the problems of transplant biology. host disease). Tolerance can be achieved with delays of up to 4 The contribution of Medawar to the understanding of the months between completion of total lymphoid irradiation and allograft rejection problem began intensive work on means to placement of the organ graft provided booster doses are given avoid rejection, including total body irradiation, marrow transduring the waiting period. The most successful protocol in plantation, purine analogues and use of corticosteroids. The baboons has involved a low cumulative dose (800 cGy), twice a latter agents were shown to prolong kidney grafts and reverse week fractionation regimen of irradiation (80 to 100 cGy each). acute rejection. The use of antilymphocyte globulin was another Up to two-thirds of the baboons so treated are rendered toler- step in the management of the rejection problem. This globulin, ant. however, occasionally resulted in thrombocytopenia, while the The role of adjuvant immunosuppressive drug therapy in purine analogues produced marrow destruction and iiver damincreasing the tolerance fraction obtained currently is under age. Although still used corticosteroids in large doses produced evaluation. Encouraging results with the use of several methods cushingoid features, aseptic necrosis of bone and delayed wound of total lymphoid irradiation in clinical renal transplantation healing. Cyclosporin A has offered a significant advance in are emerging from 5 centers. The prospect of achieving trans- immunosuppression but nephrotoxicity that is only partially plantation tolerance with total lymphoid irradiation in the reversible is being noted. Higher doses produce significant clinical context may be realized with further experience and structural renal damage. Of greatest advantage is that the drug modification of techniques. P. R. R. is effective without the use of steroids. 1 figure, 2 tables, 47 references A summary of the current results of organ transplantation is presented. In kidney transplants identical twin grafts have been effective without rejection for more than 25 years. Identically Renal Transplantation in the Diabetic matched siblings have a 90 per cent 5-year survival rate, while R. J. ROHRER, P. N. MADRAS, A. I. SAHYOUN AND A. P. poorly matched siblings or parent donor kidneys have a 70 per MONACO, Division of Organ Transplantation, Department of cent 5-year survival rate. The 5-year survival rates associated Surgery, Harvard Medical School and the New England Dea- with the use of cyclosporin A have not been tabulated to date. The results of liver transplantation have improved in the last coness Hospital, Boston, Massachusetts few years with the use of cyclosporin A. About 70 per cent of World J. Surg., 10: 397-403 (June) 1986 the children and 60 per cent of the adults will survive for 1 The results of 144 transplants performed in 134 diabetic year. The longest survival is 14 years. The heart, alone and with the lungs, has been transplanted, patients at the New England Deaconess Hospital since 1980 with the heart-lung transplants doing best. The results are are shown in tabular form. These results are similar to those comparable to those obtained with kidney transplants. in 120 nondiabetic transplant recipients from the same period, Overcoming the technical problems of pancreatic transplanalthough the 5-year patient survival rates tended to be higher in the nondiabetic recipients. With special attention to periop- tation has held the 1-year survival rate to 38 per cent. The future of organ transplantation will depend on the erative cardiovascular status, operative mortality (30 days) can development of less toxic immunosuppressive agents and better be less than 3.5 per cent and morbidity can be minimized. Living related donors continue to offer advantages in terms of methods of organ preservation. The author reflects on the organ availability and early postoperative as well as long-term problems of animal experimentation, the demand for donors, function. However, in the era of cyclosporin cadaver renal and the related moral and legal questions that can arise. J. A. transplants have evolved, with competitive 1-year patient sur- A. 4 figures vival rates of 96 per cent and 1-year graft survival rates of 88 per cent. The proportion of graft losses owing to patient death of nonimmunological causes, chiefly cardiac and cerebrovascular events, still remains relatively high at 35.8 per cent in the Complications of Cyclosporin Therapy diabetic recipient. Although rehabilitation of the diabetic paB. KAHAN, S. M. FLECHNER, M. I. LORBER, C. JENSEN, D. tient after transplantation is less complete than that of the GOLDEN AND C. T. VAN BUREN, Division of Immunology and nondiabetic transplant recipient, it clearly is superior to that Organ Transplantation, Department of Surgery, The Univerof alternative modes of therapy for the uremic diabetic pasity of Texas Medical School at Houston, Houston, Texas tient. P. R. R. 3 tables, 20 references World J. Surg., 10: 348-360 (June) 1986
1157
Total Lymphoid Irradiation in Renal Transplantation
Organ Transplantation: From Laboratory to Clinic
J. A. MYBURGH, J. A. SMIT, A. M. MEYERS, J. R. BOTHA, S. BROWDE AND P. D. THOMSON, Transplantation Research Unit, Department of Surgery, and Departments of Medicine, Radiotherapy and Pediatrics, University of the Witwatersrand and the Johannesburg Hospital, Johannesburg, South Africa
R. Y. CALNE, Department of Surgery, University of Cambridge Clinical School, Cambridge, England
Brit. Med. J., 291: 1751-1754 (Dec. 21) 1985
The author reports on the evolution of organ transplantation the early work of Hume on the kidney to current problems from World J. Surg., 10: 369-380 (June) 1986 with pancreatic transplantation. A succinct history of the Total lymphoid irradiation is a uniquely powerful method of Hume-Merrill experience with renal transplantation of kidneys producing transplantation tolerance. For tolerance production taken from dead donors or "free" kidneys (those removed with total lymphoid irradiation alone in the baboon a wide field during the course of other operations) is presented. The longest of irradiation, involving subtotal bone marrow irradiation as survival was only 5½ months but little, if any, steroids were well as lymphoid irradiation, is essential. Donor bone marrow used as an immunosuppressive agent. Transplantation between injection is not necessary for tolerance production with pri- identical twins was so successful that added impetus was given marily vascularized organ grafts (hence no risk of graft versus to understanding the problems of transplant biology. host disease). Tolerance can be achieved with delays of up to 4 The contribution of Medawar to the understanding of the months between completion of total lymphoid irradiation and allograft rejection problem began intensive work on means to placement of the organ graft provided booster doses are given avoid rejection, including total body irradiation, marrow transduring the waiting period. The most successful protocol in plantation, purine analogues and use of corticosteroids. The baboons has involved a low cumulative dose (800 cGy), twice a latter agents were shown to prolong kidney grafts and reverse week fractionation regimen of irradiation (80 to 100 cGy each). acute rejection. The use of antilymphocyte globulin was another Up to two-thirds of the baboons so treated are rendered toler- step in the management of the rejection problem. This globulin, ant. however, occasionally resulted in thrombocytopenia, while the The role of adjuvant immunosuppressive drug therapy in purine analogues produced marrow destruction and iiver damincreasing the tolerance fraction obtained currently is under age. Although still used corticosteroids in large doses produced evaluation. Encouraging results with the use of several methods cushingoid features, aseptic necrosis of bone and delayed wound of total lymphoid irradiation in clinical renal transplantation healing. Cyclosporin A has offered a significant advance in are emerging from 5 centers. The prospect of achieving trans- immunosuppression but nephrotoxicity that is only partially plantation tolerance with total lymphoid irradiation in the reversible is being noted. Higher doses produce significant clinical context may be realized with further experience and structural renal damage. Of greatest advantage is that the drug modification of techniques. P. R. R. is effective without the use of steroids. 1 figure, 2 tables, 47 references A summary of the current results of organ transplantation is presented. In kidney transplants identical twin grafts have been effective without rejection for more than 25 years. Identically Renal Transplantation in the Diabetic matched siblings have a 90 per cent 5-year survival rate, while R. J. ROHRER, P. N. MADRAS, A. I. SAHYOUN AND A. P. poorly matched siblings or parent donor kidneys have a 70 per MONACO, Division of Organ Transplantation, Department of cent 5-year survival rate. The 5-year survival rates associated Surgery, Harvard Medical School and the New England Dea- with the use of cyclosporin A have not been tabulated to date. The results of liver transplantation have improved in the last coness Hospital, Boston, Massachusetts few years with the use of cyclosporin A. About 70 per cent of World J. Surg., 10: 397-403 (June) 1986 the children and 60 per cent of the adults will survive for 1 The results of 144 transplants performed in 134 diabetic year. The longest survival is 14 years. The heart, alone and with the lungs, has been transplanted, patients at the New England Deaconess Hospital since 1980 with the heart-lung transplants doing best. The results are are shown in tabular form. These results are similar to those comparable to those obtained with kidney transplants. in 120 nondiabetic transplant recipients from the same period, Overcoming the technical problems of pancreatic transplanalthough the 5-year patient survival rates tended to be higher in the nondiabetic recipients. With special attention to periop- tation has held the 1-year survival rate to 38 per cent. The future of organ transplantation will depend on the erative cardiovascular status, operative mortality (30 days) can development of less toxic immunosuppressive agents and better be less than 3.5 per cent and morbidity can be minimized. Living related donors continue to offer advantages in terms of methods of organ preservation. The author reflects on the organ availability and early postoperative as well as long-term problems of animal experimentation, the demand for donors, function. However, in the era of cyclosporin cadaver renal and the related moral and legal questions that can arise. J. A. transplants have evolved, with competitive 1-year patient sur- A. 4 figures vival rates of 96 per cent and 1-year graft survival rates of 88 per cent. The proportion of graft losses owing to patient death of nonimmunological causes, chiefly cardiac and cerebrovascular events, still remains relatively high at 35.8 per cent in the Complications of Cyclosporin Therapy diabetic recipient. Although rehabilitation of the diabetic paB. KAHAN, S. M. FLECHNER, M. I. LORBER, C. JENSEN, D. tient after transplantation is less complete than that of the GOLDEN AND C. T. VAN BUREN, Division of Immunology and nondiabetic transplant recipient, it clearly is superior to that Organ Transplantation, Department of Surgery, The Univerof alternative modes of therapy for the uremic diabetic pasity of Texas Medical School at Houston, Houston, Texas tient. P. R. R. 3 tables, 20 references World J. Surg., 10: 348-360 (June) 1986