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2-Chlorodeoxyadenosine (Cladribine) in Combination with Low-Dose Cyclosporin Prevents Rejection after Allogeneic Heart and Liver Transplantation in the Rat

The purine analogue 2-chlorodeoxyadenosine (2-CDA) has been shown to possess synergistic immunosuppressive properties when given together with cyclosporin (CSA) in a rat small bowel transplant model. The present study investigated the immunosuppressive potency of 2-CDA alone and in combination after liver or heart transplantation in a fully allogeneic rat model with 5 animals in each group. Immunosuppression was provided with CSA 10 mg/kg body weight (BW)/day orally or 2-CDA 0.1 mg/kg/BW day intravenously or both compounds together in the dosages mentioned. Animals were sacrificed on day 10 following transplantation, and graft histology was assessed. In addition, cardiac graft function was evaluated by palpation immediately prior to sacrificing the animal. CSA given alone was able to mitigate but not prevent rejection. 2-CDA alone did not exhibit any detectable immunosuppressive effect. When CSA was combined with 2-CDA, no rejection was seen in 80% of the liver allografts and in 60% of heart allografts, and only mild rejection was observed in the remaining animals. All hearts of the combined treatment group, however, beat strongly. From these findings it is concluded that 2-CDA alone has no, but together with CSA a strong immunosuppressive effect in preventing solid organ allograft rejection.