Manuelli M, De Luca L, Iaria G, Tatangelo P, Sforza D, Perrone L, Bellini M I, Angelico R, Anselmo A, Tisone G
Transplant Unit, Università Tor Vergata, Ospedale S Eugenio, Rome, Italy.
Transplant Proc. 2010 May;42(4):1314-6. doi: 10.1016/j.transproceed.2010.03.051.
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.
Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6).
Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up.
Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.
恶性肿瘤是肾移植受者免疫抑制治疗的一种众所周知的并发症,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。
15例患者在肾移植后平均90.3个月(范围=10 - 252个月)发生了以下恶性肿瘤: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 = 2)、卡波西肉瘤(n = 2)、移植后淋巴细胞增殖性疾病(PTLD;n = 4)、肾细胞癌T1(n = 1)、黏膜相关淋巴组织淋巴瘤(n = 1)、黏膜内结肠癌(n = 1)、精索脂肪肉瘤(n = 1)。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治疗转换为雷帕霉素治疗(单药治疗,n = 3),或与类固醇联合使用(n = 6)或与霉酚酸酯联合使用(n = 6)。
两名转移性癌症患者均接受了化疗,但分别在6个月和13个月后死亡。两名接受化疗的PTLD患者分别在12个月和36个月后死亡。在平均32.7个月(范围=7 - 56个月)的随访中,其余11例患者无癌症。两名患者在转换治疗后24个月和36个月因慢性排斥反应失去了移植肾。从诊断到随访结束,所有其他患者的移植肾功能保持稳定。
我们的观察结果表明,基于雷帕霉素的免疫抑制治疗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由于雷帕霉素治疗还是免疫抑制的降低。