Survival of primates following orthotopic cardiac transplantation treated with total lymphoid irradiation and chemical immune suppression.
Fractionated total lymphoid irradiation (TLI) has been used for attempts at induction of a donor-specific tolerant-like state in allograft recipients and for immunosuppressive effects. Cyclosporin A (Cy A) has been shown to suppress rejection of organ grafts in many species including man. The present study was designed to test the effectiveness of TLI in combination with either CY A or rabbit anticynomolgus thymocyte globulin (ATG) and azathioprine. Thirty-one orthotopic cardiac allografts were performed using surface cooling and total circulatory arrest in outbred cynomolgus monkeys. TLI was administered preoperatively in fractions of 100 rad until a total of 600 or 1800 rad was achieved. Cy A was administered 17 mg/kg/day. All treatment groups demonstrated extended survival. Myocardial biopsies as early as 4 weeks were consistent with mild rejection in all treatment groups. No significant synergistic effect upon survival could be demonstrated utilizing TLI plus Cy A when compared with using Cy A alone. TLI (1800 rad) plus ATG and azathioprine was associated with a high incidence of early death attributable to leukopenia and infection. Cy A alone or in combination with TLI was associated with the development of lymphoid malignancy.
D000818:Animals; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001379:Azathioprine / Q000627:therapeutic use; D003524:Cyclosporins / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000187:drug effects; D016027:Heart Transplantation; D008221:Lymphoid Tissue / Q000528:radiation effects*; D008251:Macaca / Q000276:immunology*; D008252:Macaca fascicularis / Q000276:immunology*; D008297:Male; D013514:Surgical Procedures, Operative / Q000401:mortality*; D014965:X-Rays
D000961:Antilymphocyte Serum; D003524:Cyclosporins; D001379:Azathioprine