Lauro A, Dazzi A, Ercolani G, Zanfi C, Golfieri L, Amaduzzi A, Cucchetti A, La Barba G, Grazi G L, D'Errico A, Vivarelli M, Cescon M, Varotti G, Del Gaudio M, Ravaioli M, Di Simone M, Faenza S, Pironi L, Pinna A D
U.O. Chirurgia dei Trapianti di Fegato e Multiorgano, University of Bologna, Policlinico S. Orsola-Malpighi, Massarenti no. 9, Bologna 40138, Italy.
Transplant Proc. 2007 Jun;39(5):1629-31. doi: 10.1016/j.transproceed.2007.02.067.
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.
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).
During prolonged treatment combined with Tacrolimus (Prograf), both Sirolimus 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).
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.
雷帕霉素哺乳动物靶点(mTOR)抑制剂最近已被引入肠道移植后的临床实践。我们聚焦于西罗莫司(雷帕霉素),以研究其对肠道移植后排斥反应和移植物存活的影响。
我们系列中的20例孤立性肠道移植受者和5例多脏器移植患者(2例合并肝脏移植)被分为3组:因肾毒性或活检证实的排斥反应而开始使用西罗莫司且持续治疗超过3个月的患者(n = 11);因肾毒性或活检证实的排斥反应而开始使用西罗莫司但因副作用接受治疗少于3个月的患者(n = 4);以及从未接受过雷帕霉素治疗的对照组(n = 10)。
在与他克莫司(普乐可复)联合进行的长期治疗期间,两个西罗莫司组的急性细胞排斥反应数量均减少(P <.01)。西罗莫司治疗超过3个月组的3年移植物和患者累积生存率分别为81%,西罗莫司治疗少于3个月组为100%,对照组分别为80%和90%(P =.63和P =.62)。
根据我们的经验,mTOR抑制剂与钙调神经磷酸酶抑制剂联合使用似乎比单一疗法在减少排斥反应数量方面更有效。副作用可能会限制其作为维持治疗的应用。