Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies
Maintenance immunosuppression with target-of-rapamycin inhibitors is associated with a reduced incidence of de novo malignancies
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DOI：
10.1097/01.tp.0000184006.43152.8d
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发表时间：
2005-10-15
期刊：
影响因子：
6.2
通讯作者：
Kahan, BD
中科院分区：
文献类型：
--
作者：
Kauffman, HM;Cherikh, WS;Kahan, BD
背景。免疫抑制药物治疗已被确定为肾移植受者恶性肿瘤发病率增加和死亡的一个病因因素。在动物模型中，钙调神经磷酸酶抑制剂对恶性细胞有促进生长的作用，而雷帕霉素靶蛋白（TOR）抑制剂则有抑制生长的作用。
方法。对1996年7月1日至2001年12月31日期间264个肾移植项目向器官获取与移植网络数据库报告的33249名尸体供体原发性孤立肾受者的移植后恶性肿瘤进行多变量分析。数据在963天进行审查，以便在药物治疗组之间有可比的随访时间。主要终点是接受TOR抑制剂的患者与接受钙调神经磷酸酶抑制剂的患者相比，任何新发恶性肿瘤（皮肤和实体）以及非皮肤实体恶性肿瘤的发病率和相对风险。
结果。仅使用西罗莫司/依维莫司的患者移植后任何新发恶性肿瘤的发病率为0.60%，使用西罗莫司/依维莫司 + 环孢素/他克莫司的患者为0.60%，使用环孢素/他克莫司的患者为1.81%（P < 0.0001）；新发实体瘤的发病率分别为0%、0.47%和1.00%。在Cox回归模型中，西罗莫司/依维莫司免疫抑制与任何新发癌症相关的相对风险为0.39（95%置信区间：0.24 - 0.64；P = 0.0002），与新发实体癌相关的相对风险为0.44（0.24 - 0.82；P = 0.0092）。其他显著的风险因素是男性、成年年龄组、白人种族和恶性肿瘤病史。
结论。使用TOR抑制剂药物西罗莫司和依维莫司进行维持性免疫抑制与移植后发生任何新发恶性肿瘤和非皮肤实体恶性肿瘤的风险显著降低有关。
Background. Immunosuppressive drug therapy has been identified as one etiological factor in the increased incidence of and deaths from malignancies in renal transplant recipients. In animal models, calcineurin inhibitors have a positive growth effect, whereas target- of-rapamycin (TOR) inhibitors have a negative growth effect on malignant cells.Methods. A multivariate analysis of posttransplant malignancies in 33,249 deceased donor primary solitary renal recipients reported by 264 kidney transplant programs to the Organ Procurement and Transplantation Network database from July 1, 1996 to December 31, 2001 was performed. Data were censored at 963 days to allow comparable follow-up time among drug treatment groups. The incidence and relative risks of any de novo malignancy (skin and solid) and for nonskin solid malignancies in patients receiving TOR inhibitors compared to patients receiving calcineurin inhibitors were the primary endpoints.Results. The incidence rates of patients with any de novo posttransplant malignancy were 0.60% with sirolimus/ everolimus alone, 0.60% with sirolimus/everolimus + cyclosporine/tacrolimus, and 1.81% with cyclosporine/tacrolimus (P < 0.0001); the rates with a de novo solid tumor were 0%, 0.47%, and 1.00%, respectively. In the Cox regression model the relative risk associated with sirolimus/everolimus immunosuppression for any de novo cancer was 0.39 (95% Cl: 0.24-0.64; P=0.0002) and for de novo solid cancer was 0.44 (0.24-0.82; P=0.0092). Other significant risk factors were mate sex, adult age group, white race, and history of a malignancy.Conclusions. Maintenance immunosuppression with the TOR inhibitor drugs, sirolimus and everolimus, is associated with a significantly reduced risk of developing any posttransplant de novo malignancy and nonskin solid malignancy.