Iaria G, Anselmo A, De Luca L, Manuelli M, Lucchesi C, Tariciotti L, Monaco A, Sforza D, Nigro F, Abruzzese E, Tisone G
Clinica Chirurgica AS Trapianti, Università Tor Vergata Ospedale S Eugenio, Roma, Italy.
Transplant Proc. 2007 Jul-Aug;39(6):2036-7. doi: 10.1016/j.transproceed.2007.05.046.
Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro.
Eight patients developed the following malignancies after kidney transplantation (mean 102.6 months; range 12 to 252): metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 1), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD) (n = 2). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 2), associated with steroids (n = 4) or mycophenolate mofetil (n = 2).
Both patients with metastatic cancer underwent chemotherapy and then succummbed after 6 and 13 months. After a mean follow-up of 20.3 months (range 2 to 47), the remaining six patients are free from cancer disease. Renal graft function was unchanged from diagnosis throughout the follow-up.
Our observations suggested that rapamycin-based immunosuppression offered the possibility of regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was attributed to Rapamycin treatment or to the reduced immunosuppression.
恶性肿瘤是肾移植受者免疫抑制治疗中众所周知的并发症,是长期发病和死亡的重要原因。雷帕霉素已被证明在体内和体外均可限制多种恶性细胞系的增殖。
8例患者在肾移植后发生了以下恶性肿瘤(平均102.6个月;范围12至252个月):转移性胃癌(n = 1)、转移性结肠癌(n = 1)、双侧肾盂尿路上皮癌(n = 1)、皮肤癌(n = 1)、卡波西肉瘤(n = 2)、移植后淋巴细胞增殖性疾病(PTLD)(n = 2)。在诊断为恶性肿瘤后,患者从基于钙调神经磷酸酶抑制剂的免疫抑制转换为雷帕霉素(单药治疗,n = 2),联合使用类固醇(n = 4)或霉酚酸酯(n = 2)。
两名转移性癌症患者均接受了化疗,然后分别在6个月和13个月后死亡。在平均随访20.3个月(范围2至47个月)后,其余6名患者无癌症疾病。在整个随访过程中,肾移植功能自诊断后未发生变化。
我们的观察结果表明,基于雷帕霉素的免疫抑制为非转移性肿瘤的消退提供了可能性。然而,很难评估肿瘤消退是归因于雷帕霉素治疗还是免疫抑制的降低。