DLA-IDENTICAL BONE-MARROW GRAFTS AFTER LOW-DOSE TOTAL-BODY IRRADIATION - EFFECTS OF HIGH-DOSE CORTICOSTEROIDS AND CYCLOSPORINE ON ENGRAFTMENT

Previous studies found that marrow allografts from DLA-identical litte rmates resulted in survival of 60% of recipient dogs after an otherwis e lethal dose of 450 cGy of total body irradiation (TBI). either becau se of successful allografts or autologous recovery after rejection of the allografts. Forty percent of dogs died with marrow aplasia after a llograft rejection. The current study asked whether allogeneic engraft ment could be enhanced and survival improved by treating allograft rec ipients with high doses of corticosteroids or with cyclosporine (CSP), administered either before or after transplantation. Five dogs in gro up 1 received corticosteroids beginning on day -5 and ending on day 32 after transplant. The starting dose was 12.5 mg of prednisone per kil ogram orally twice daily. All five dogs rejected their allografts; thr ee died early with marrow aplasia and two showed endogenous marrow rec overy. Nine dogs received CSP from day -6 to day -1 before transplanta tion at a dose of 20 mg/kg/d intravenously administered in divided dos es. All nine dogs rejected the marrow allograft; six died with marrow aplasia and three survived with endogenous marrow recovery. Seven dogs received CSP after transplantation at a dose of 30 mg/kg/d orally fro m day -1 to day 35. All seven had sustained allografts (two mixed chim eras and five complete donor-type chimeras) and became healthy longter m survivors without graft-versus-host disease. These results extend pr evious observations and confirm that grafts of marrow from DLA-identic al littermates improved survival of dogs exposed to low but otherwise lethal doses of TBI. Additional therapy with high-dose corticosteroids administered peritransplantation and posttransplantation or CSP admin istered before transplantation neither enhanced the rate of allogeneic engraftment nor improved survival; however, CSP administered after tr ansplantation resulted in successful allografts and event-free surviva l in all cases. (C) 1995 by The American Society of Hematology.