Safety of an immunosuppressant protocol based on sirolimus in liver transplant recipients with malignancies or high risk of tumor recurrence.

BACKGROUND

The mammalian target of rapamycin inhibitors are immunosuppressive agents with antiproliferative effects and consequent potential application as anticancer agents. The safety and tolerance of calcineurin inhibitor (CNI)-free sirolimus-based immunosuppressant protocols in liver transplant recipients with malignancies or high risk of tumor recurrence has been scarcely evaluated.

PATIENTS AND METHODS

Fourteen liver transplant recipients, including 12 men, of overall mean age of 57.4 +/- 12.4 years were distributed into two groups: group I, corresponding to 11 patients with malignant neoplasia, eight de novo neoplasia, and three recurrent hepatocarcinoma and; group II, three patients with high risk of tumor recurrence due to cholangiocarcinoma. Sirolimus was initiated at 2 mg od, with target levels of 3 to 9 ng/mL. Withdrawal of CNI was performed after reaching target levels of sirolimus. Periodic examinations of weight, arterial pressure, liver function tests, serum creatinine, triglycerides, cholesterol, sirolimus blood levels, and creatinine clearance were performed at 30, 60, 90, 180, and 360 days.

RESULTS

After a median follow-up of 221.5 days, eight group I patients (72.7%) were alive, including six with stable disease. All group II patients were alive without evidence of tumor recurrence after a median follow-up of 560 days. CNI was withdrawn in 11 patients (78.6%). Sirolimus was withdrawn in only one case due to severe symptomatic oral ulcers. No vascular complications or rejection episodes were observed.

CONCLUSIONS

A sirolimus-based immunosuppressant protocol was well tolerated and safe in liver transplant recipients with malignancies or a high risk of recurrence of neoplastic disease.