Alamo J M, Bernal C, Marín L M, Suárez G, Serrano J, Barrera L, Sousa J M, Padillo F J, Gómez-Bravo M A
Liver Transplant Unit, Virgen del Rocío Hospital, Seville, Spain.
Transplant Proc. 2012 Sep;44(7):2089-92. doi: 10.1016/j.transproceed.2012.07.079.
The reported incidences of de novo malignancy following orthotopic liver transplantation (OLT) are significantly greater than those in the general population. We have analyzed the efficacy of mammalian target of rapamycin inhibitor (mTORi) as immunosuppressant therapy in patients with de novo malignancies or those engrafted because of a primary liver cancer.
We performed a case-control study of patients with hepatocellular carcinoma (HCC; n = 119), cholangiocarcinoma (n = 1) or de novo malignancies (n = 73). Thirty-seven patients with these tumors were treated with mTORi, and 167, with calcineurin inhibitors (CNI). Switching to mTORi was performed progressively, withdrawing the CNI over 15 days, until obtaining levels of 5-10 ng/dL.
No incidence of rejection, serious adverse events, or death was observed with an overall actuarial survival of 68.5% in the mTORi group versus 45.7% among the CNI group. Overall rates of tumor recurrence were 15.2% and 36.8%, respectively (P < .05). Among patients with HCC, survival was 100% of mTORi with and 61.5% among CNI patients, with tumor recurrence rates of 6.2% and 19.1%, respectively (P < .05).
Surprising differences in survival and tumor recurrence rates were observed among the mTORi-treated group compared with controls. Switching from CNI to mTORi immunosuppressant therapy appeared to be safe. It seems to be reasonable to employ this strategy in liver transplant patients with primary hepatic or "de novo" neoplasms.
原位肝移植(OLT)后新发恶性肿瘤的报告发病率显著高于普通人群。我们分析了雷帕霉素靶蛋白抑制剂(mTORi)作为免疫抑制疗法在新发恶性肿瘤患者或因原发性肝癌而接受移植患者中的疗效。
我们对肝细胞癌(HCC;n = 119)、胆管癌(n = 1)或新发恶性肿瘤(n = 73)患者进行了病例对照研究。37例患有这些肿瘤的患者接受了mTORi治疗,167例接受了钙调神经磷酸酶抑制剂(CNI)治疗。逐渐改用mTORi,在15天内停用CNI,直至达到5 - 10 ng/dL的水平。
未观察到排斥反应、严重不良事件或死亡的发生,mTORi组的总精算生存率为68.5%,而CNI组为45.7%。肿瘤复发的总体发生率分别为15.2%和36.8%(P < 0.05)。在HCC患者中,mTORi治疗组的生存率为100%,CNI治疗组为61.5%,肿瘤复发率分别为6.2%和19.1%(P < 0.05)。
与对照组相比,mTORi治疗组在生存率和肿瘤复发率方面存在惊人差异。从CNI转换为mTORi免疫抑制疗法似乎是安全的。在患有原发性肝脏或“新发”肿瘤的肝移植患者中采用这种策略似乎是合理的。