O'Neill James O, Edwards Leah B, Taylor David O
International Society for Heart and Lung Transplantation, Addison, Texas.
J Heart Lung Transplant. 2006 Oct;25(10):1186-91. doi: 10.1016/j.healun.2006.06.010. Epub 2006 Sep 18.
Malignancy after organ transplantation has been described as the "price of immunotherapy." Evolving strategies aimed at effective immunosuppression could have differing effects on the likelihood of developing malignancy. We analyzed data from the transplant registry of the International Society for Heart and Lung Transplantation (ISHLT) to ascertain which factors are associated with the development of malignancy after orthotopic heart transplantation (OHT).
Multivariate modeling was performed to determine factors predictive of first post-transplant malignancy in patients taking standard immunosuppressive regimens, defined as cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil (MMF), who underwent OHT between January 1, 1995 and December 31, 1997.
Of the 3,895 transplants described in the cohort, 703 (18%) developed post-transplant malignancy at any time during the follow-up period, and 549 (14%) developed malignancy within the first 5 years post-transplant. The breakdown of malignancy was as follows: skin: 47%; post-transplant lymphoproliferative disease: 10%; other malignancies: 24%; combination of types: 10%; and unreported: 10%. Multivariate modeling revealed that independent predictors of increased risk were prior malignancy and increased age, whereas the use of MMF as part of a standard immunosuppressive regimen was associated with an adjusted relative risk (RR) = 0.73 (95% confidence interval 0.56 to 0.95). Relative to a recipient age of 55 years, the risk of malignancy for 30, 45 and 60 years of age was 0.32, 0.46 and 1.37, respectively. Although the use of tacrolimus appeared protective in the univariate analysis, it was not significant according to multivariate analysis. Female gender appeared to be protective. Neither OKT3 nor anti-thymocyte globulin (ATG) use was associated with a significantly increased risk of malignancy.
The choice of immunosuppressive regimen may affect the likelihood of developing malignancy after OHT. Induction immunosuppression does not appear to increase the risk of subsequent malignancy. The use of MMF in standard immunosuppressive regimens is associated with a significantly lower risk of developing malignancy.
器官移植后的恶性肿瘤被描述为“免疫治疗的代价”。旨在有效免疫抑制的不断发展的策略可能对发生恶性肿瘤的可能性产生不同影响。我们分析了国际心肺移植学会（ISHLT）移植登记处的数据，以确定哪些因素与原位心脏移植（OHT）后恶性肿瘤的发生相关。
对1995年1月1日至1997年12月31日期间接受OHT且采用标准免疫抑制方案（定义为环孢素或他克莫司以及硫唑嘌呤或霉酚酸酯（MMF））的患者进行多变量建模，以确定移植后首次发生恶性肿瘤的预测因素。
在该队列中描述的3895例移植中，703例（18%）在随访期间的任何时间发生了移植后恶性肿瘤，549例（14%）在移植后的前5年内发生了恶性肿瘤。恶性肿瘤的分类如下：皮肤：47%；移植后淋巴细胞增生性疾病：10%；其他恶性肿瘤：24%；多种类型组合：10%；未报告：10%。多变量建模显示，风险增加的独立预测因素是既往恶性肿瘤和年龄增加，而作为标准免疫抑制方案一部分使用MMF与调整后的相对风险（RR）=0.73（95%置信区间0.56至0.95）相关。相对于55岁的受者年龄，30岁、45岁和60岁发生恶性肿瘤的风险分别为0.32、0.46和1.37。虽然在单变量分析中使用他克莫司似乎具有保护作用，但根据多变量分析并不显著。女性似乎具有保护作用。使用OKT3或抗胸腺细胞球蛋白（ATG）均与恶性肿瘤风险显著增加无关。
免疫抑制方案的选择可能会影响OHT后发生恶性肿瘤的可能性。诱导免疫抑制似乎不会增加随后发生恶性肿瘤的风险。在标准免疫抑制方案中使用MMF与发生恶性肿瘤的风险显著降低相关。
