Use of Sirolimus in Lung Transplantation: A Single Center Experience

Abstract

Purpose Sirolimus is an effective immunosuppressive agent in solid organ transplantation although its use in lung transplant recipients is limited to patients more than 3 months after the procedure due to the risk of anastamotic dehiscence. Sirolimus is used as an alternative immunosuppressant in our program for the treatment of refractory rejection, bronchiolitis obliterans syndrome (BOS), and calcineurin renal intolerance. Our experience with the use of this agent is described. Methods and Materials Patients transplanted from 2000-2011 who were converted to sirolimus post-transplant were evaluated in a retrospective fashion. All patients initially received a calcineurin inhibitor (CNI), an antiproliferative agent, and prednisone. Variables examined included baseline characteristics, reason to initiate sirolimus, adverse effects (AEs), and renal function. Results 49 of 345 (14%) patients transplanted between 2000-2011 were converted to sirolimus post-transplant. Reasons for converting included development of BOS (55%), AEs of CNI (hyperkalemia, nephrotoxicity, and neurotoxicity)(22%), worsening renal function (12%), leucopenia (8%), and acute rejection (2%). Median time to conversion was 945 days (79-3756 days). Sirolimus was combined with a CNI in 47% of patients. Patients remained on sirolimus for a median of 135 days (1-3013 days). Sirolimus was discontinued in 42 patients (86%) due to AEs (55%), death (24%), infection (9%), or other reasons (12%). Most common AEs leading to discontinuation were suspected pulmonary toxicity (48%), thrombocytopenia (13%), anemia (9%), and delayed wound healing (9%). Renal function declined after the initiation of sirolimus to its discontinuation (mean 62 ml/min v. 58 ml/min (sirolimus alone) and 56 ml/min (sirolimus with CNI)). Conclusions Our single center experience demonstrates a high discontinuation rate of sirolimus in lung transplant recipients due to its numerous adverse effects. The utility of sirolimus for preventing allograft rejection is overshadowed by its toxicity which should be considered prior to its initiation.