Shaw Reid, Haque Ali R, Luu Tyler, O'Connor Timothy E, Hamidi Adam, Fitzsimons Jack, Varda Bianca, Kwon Danny, Whitcomb Cody, Gregorowicz Alex, Roloff Gregory W, Bemiss Bradford C, Kallwitz Eric R, Hagen Patrick A, Berg Stephanie
Department of Internal Medicine, Loyola University Medical Center, Maywood, United States.
Department of Pharmacy, Hines Veterans Affairs Hospital, Hines, United States.
Front Oncol. 2023 Jun 16;13:1146002. doi: 10.3389/fonc.2023.1146002. eCollection 2023.
This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types.
This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy.
A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia.
Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients.
本研究旨在评估维持性免疫抑制对所有实体器官移植类型移植后发生恶性肿瘤风险的影响。
这是一项来自美国多中心医院系统的回顾性队列研究。从2000年至2021年查询电子健康记录，以获取实体器官移植病例、免疫抑制药物使用情况及移植后恶性肿瘤情况。
共识别出5591例患者、6142个移植器官以及517例移植后恶性肿瘤。皮肤癌是最常见的恶性肿瘤类型，占52.8%，而肝癌是移植后最早出现的恶性肿瘤，中位出现时间为移植后351天。心脏和肺移植受者的恶性肿瘤发生率最高，但在调整免疫抑制药物后这一发现无统计学意义（心脏：风险比[HR]0.96，95%置信区间[CI]0.72 - 1.3，p = 0.88；肺：HR 1.01，95% CI 0.77 - 1.33，p = 0.94）。随机森林变量重要性计算和时间依赖性多变量Cox比例风险分析表明，接受西罗莫司免疫抑制治疗的患者患癌风险增加（HR 1.41，95% CI 1.05 - 1.9，p = 0.04），接受硫唑嘌呤治疗的患者患癌风险增加（HR 2.1，95% CI 1.58 - 2.79，p < 0.001），接受环孢素治疗的患者患癌风险增加（HR 1.59，95% CI 1.17 - 2.17，p = 0.007），而他克莫司（HR 0.59，95% CI 0.44 - 0.81，p < 0.001）与移植后肿瘤形成率较低相关。
我们的结果显示，免疫抑制药物与移植后恶性肿瘤发生风险存在差异，这表明实体器官移植受者癌症检测和监测策略的重要性。
