P0250* SAFETY AND EFFICACY OF SIROLIMUS IN CHILDREN FOLLOWING CHRONIC REJECTION AND/OR NEPHROTOXICITY POST INTESTINAL TRANSPLANT (ITX) AND LIVER TRANSPLANTATION (LTX).

Abstract

Introduction: Chronic rejection after transplantation and drug induced nephrotoxicity continue to be major clinical problems. Sirolimus is a potent immunosuppressant acting on the mTOR receptor with no adverse effects on renal function. AIM To evaluate the safety and efficacy of Sirolimus in intestinal transplantation (ITx) and liver (LTx) transplant recipients in children. Methods: Retrospective review from Jan ’01 to Dec ’02. 14 children (9M): renal toxicity (n=5);recurrent rejection/acute steroid resistant rejection after ITx and/or LTx (n=9) were included. Results: Median age at transplant (Tx): 34 months. Median time post Tx at starting Sirolimus: 41.8 months. Sirolimus treatment followed up for 100–500 days. Patients receiving Sirolimus due to nephrotoxicity showed an improvement in cGFR from 52 to 73 ml/ml/1.73m2. Liver function tests improved in those with recurrent rejection and small bowel allograft function. Table 1 summarises data on efficacy and safety of Sirolimus. Adverse events: Infection: pneumonia (7 episodes), adenovirus (1), Influenza (1), EBV viraemia (4) and staphylococcus (2). Two children developed mucosal lesions, buccal mucosal ulcer (1) and candidial oesophageal lesions (1). 3 patients developed high triglycerides not requiring treatment. 5 children experienced transient thrombocytopaenia. Sirolimus temporarily withheld for EBV viraemia (1) and discontinued(1)for protracted neutropenia. Two patients with intestinal graft died after 8m and 15m exposure to Sirolimus (bowel perforation and fungal endocardititis).Table 1Conclusion: Sirolimus as a concomitant immunosuppressant is effective in acute steroid resistant and chronic rejection for ITx/LTx recipients. We recommend caution in the long term use of Sirolimus in ITx recipients