EFFECT OF RAPAMYCIN ON RENAL-ALLOGRAFT SURVIVAL IN CANINE RECIPIENTS TREATED WITH ANTILYMPHOCYTE-SERUM, DONOR BONE-MARROW, AND CYCLOSPORINE

Rapamycin (Rapa) monotherapy can promote renal allograft survival in d ogs, but it is very toxic. To attempt to augment the effectiveness of Rapa and reduce its toxicity in a tolerance induction protocol, canine renal allograft recipients were treated briefly with antilymphocyte s erum (ALS), donor bone marrow cells (BMC), and a limited course of cyc losporine (CsA). Rapa had little effect when CsA-treated recipients we re given ALS on days -5 to -1 and BMC on day +1. When combined with Cs A given days +13 to +42, ALS on days -5 to +7, and BMC on day +10, Rap a at 0.3 mg/kg on day +8 plus alternate days +15 to +39 significantly increased overall survival and was compatible with long-term survival after immunosuppression (6 grafts, 1 graft >212 days, 1 graft >470 day s). Rapa appeared to prevent early rejections that can occur during tr eatment with these ALS/BMC/CsA protocols. Little toxicity of Rapa was observed with any treatment.