Rejection Episodes and 3-Year Graft Survival Under Sirolimus and Tacrolimus Treatment After Adult Intestinal Transplantation A. Lauro, A. Dazzi, G. Ercolani, C. Zanfi, L. Golfieri, A. Amaduzzi, A. Cucchetti, G. La Barba, G.L. Grazi, A. D’Errico, M. Vivarelli, M. Cescon, G. Varotti, M. Del Gaudio, M. Ravaioli, M. Di Simone, S. Faenza, L. Pironi, and A.D. Pinna ABSTRACT Purpose. Mammalian target of rapamycin (mTOR) inhibitors have been recently introduced in clinical practice after intestinal transplantation. We focused on Sirolimus (Rapamycin) to examine effects on rejection and graft survival following intestinal transplantation. Patients and methods. Twenty isolated intestinal recipients and 5 multivisceral patients (2 with liver) in our series were divided into 3 groups: patients started on Sirolimus (because of nephrotoxicity or biopsy-proven rejection), who continued therapy longer than 3 months (n = 11); patients started on Sirolimus (because of nephrotoxicity or biopsy- proven rejection), who received therapy less than 3 months because of side effects (n = 4); and a control group, who never received rapamycin (n = 10). Results. During prolonged treatment combined with Tacrolimus (Prograf), both Siroli- mus groups showed a decreased number of acute cellular rejections (P  .01). Cumulative 3-year graft and patient survival rates were 81% in the Sirolimus greater than 3 months group, 100% in the Sirolimus less than 3 months group, and 80% and 90% in the control group, respectively (P = .63 and P = .62). Conclusion. In our experience, the use of mTOR-inhibitors in combination with calcineurin-inhibitors seemed to be more effective than monotherapy to reduce the number of rejections. Side effects can limit its use as maintenance therapy. S IROLIMUS, an immunosuppressive agent purified from soil Streptomyces hygroscopicus limits the ability of T lymphocytes to replicate. The efficacy of Sirolimus (Rapamycin) as primary immunosuppression with Tacroli- mus (Prograf) has been proven after renal, pancreas, and liver transplantation 1 and recently after intestinal trans- plantation. 2,3 Reviewing our experience in intestinal and multivisceral transplantation with Sirolimus, we focused on its effects as adjuvant therapy as well as side effects. PATIENTS AND METHODS Between December 2000 and January 2005, we performed 27 intestinal transplantations on patients with life- threatening com- plications related to parenteral nutrition: 20 isolated intestinal and 5 multivisceral (2 with liver) recipients were divided into 3 groups. Eleven recipients were started on Sirolimus because of nephrotox- icity or biopsy-proven rejection (Sirolimus longer than 3 months group first group). Four patients received Sirolimus for less than 3 months (Sirolimus less than 3 months group second group). Sirolimus was administered with a 5 mg/m 2 loading dose, followed by a 2 mg/m 2 maintenance dose to keep a level between 5 and 10 g/mL. Sirolimus blood level was tested weekly. In the first group, the male/female ratio was 4/7 with a mean age at transplantation of 37.7 years. Primary diseases were as follows: short bowel syndrome (n = 6), chronic intestinal pseudo-obstruction (n = 3), Gardner’s syndrome (n = 1), and radiation enteritis (n = 1). In the second group, the male/female ratio was 2/2 with a mean age at transplan- From the U.O. Chirurgia dei Trapianti di Fegato e Multiorgano (A.L., A.D., G.E., C.Z., L.G., A.A., A.C., G.L.B., G.L.G., M.V., M.C., G.V., M.D.G., M.R., M.D.S., S.F., A.D.P.), Anatomia e Istologia Patologica-Istituto F. Addarii (A.D.E.), and Centro di Riferimento Insufficienza Intestinale (L.P.), University of Bologna, Policlinico S. Orsola-Malpighi, Bologna, Italy. Address reprint requests to Augusto Lauro, MD, U.O. Chiru- rgia dei Trapianti di Fegato e Multiorgano, University of Bologna, Massarenti n. 9, Bologna 40138, Italy. E-mail: augustola@yahoo. com © 2007 by Elsevier Inc. All rights reserved. 0041-1345/07/$–see front matter 360 Park Avenue South, New York, NY 10010-1710 doi:10.1016/j.transproceed.2007.02.067 Transplantation Proceedings, 39, 1629 –1631 (2007) 1629