Cyclosporin A in clinical organ grafting. First Northern Ireland Kidney Research Fund lecture.

FOLLOWING Borel's description of a new immunosuppressive agent, a fungal cyclic peptide, Cyclosporin A (CyA), which had immunosuppressive action 1 a number of experimental papers demonstrated that the agent was a potent inhibitor of rejection of organ allografts in a variety of species 2, 3, 4, 5, 6, 7, 8. Green and Allison 9 found that a short period of treatment with CyA given to rabbits with renal allografts could be followed by prolonged acceptance of the transplant and suggested that CyA might be eliminating clones of lymphocytes reactive against the allograft in question. The mode of action of CyA is not understood but there is agreeinent by independent workers that the agent is more active against proliferating T-cells than other members of the lymphoid series 10, 11, 12. We have published two interim reports on a pilot study of CyA 13, 14 initially as the only immunosuppressive agent in human recipients of cadaveric organ grafts. This study has now been in progress for two years. Fifty-eight patients have received 65 cadaver organ grafts, 51 kidney grafts, eight segmental vascularised pancreas grafts and six orthotopic liver allografts. The 58 patients range in age from 2 to 59. Nineteen were over 50 years. Two renal allografts were second transplants after the first had failed for technical reasons. The remaining 62 organs were first grafts. All received organs mismatched for A and B locus antigens. In most cases there were two or more mismatches. Details of DR matching are not available. All but one of the 51 recipients with renal allografts had previously been given blood transfusions. Six of the renal allograft recipients also received segmental grafts of pancreas from the same donor. Six patients received orthotopic liver grafts. One of these also had a segmental pancreatic graft. One patient with rapidly progressive retinopathy and severely impaired vision from insulindependent diabetes received a segmental pancreas allograft alone. Of 51 patients who received renal allografts CyA was given at an initial dose of 25 mg/kg/day in seven cases, 10 mg/kg/day in four cases and 17 mg/kg/ day in the remaining forty cases.