Department of Dermatology and Venereology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
QIMR Berghofer Medical Research Institute, Cancer and Population Studies, Brisbane, Queensland, Australia.
J Heart Lung Transplant. 2018 Jul;37(7):853-859. doi: 10.1016/j.healun.2018.03.012. Epub 2018 Mar 19.
Chronic immunosuppression after solid-organ transplantation is a risk factor for cutaneous squamous cell carcinoma (cSCC) development. Certain immunosuppressant drugs, namely azathioprine and calcineurin inhibitors, increase this risk more than others. We investigated incidence of cSCC in a Dutch lung transplant recipient (LTR) cohort and analyzed associated risk factors.
All LTRs with post-transplant survival of >30 days were included. Data included indication for lung transplantation and duration of medication use. Skin cancer data were extracted from the Dutch nationwide registry of histopathology (PALGA). Uni- and multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression analyses.
Five hundred forty-four patients were included with a median survival of 11.05 years. Fifty-two (9.6%) LTRs developed at least one cSCC, with a cumulative incidence of 3.9% and 15.3% after 5 and 10 years, respectively. Multivariate analyses showed that the sequential use of azathioprine and mycophenolate mofetil (MMF), both at for least 1 year, was associated with a lower risk of developing cSCC (hazard ratio [HR] 0.24; 95% confidence interval [CI] 0.10 to 0.56) compared with azathioprine use only. Furthermore, age at transplantation (HR 3.42; 95% CI 1.33 to 8.79), male gender (HR 1.75; 95% CI 1.00 to 3.05), previous skin cancer (HR 4.75; 95% CI 1.14 to 19.76), and history of smoking (HR 3.30; 95% CI 1.69 to 6.44) were associated with increased risk of developing cSCC in univariate analyses.
Apart from known risk factors, we found that switching from azathioprine to MMF is associated with reduced incidence of cSCC in LTR, prompting a discussion of whether switching azathioprine to MMF should be considered in high-risk patients.
实体器官移植后的慢性免疫抑制是皮肤鳞状细胞癌（cSCC）发展的一个风险因素。某些免疫抑制剂药物，即硫唑嘌呤和钙调神经磷酸酶抑制剂，比其他药物更能增加这种风险。我们调查了荷兰肺移植受者（LTR）队列中 cSCC 的发病率，并分析了相关的危险因素。
所有移植后生存时间超过 30 天的 LTR 均被纳入研究。数据包括肺移植的适应证和药物使用时间。皮肤癌数据从荷兰全国组织病理学登记处（PALGA）中提取。使用 Cox 比例风险回归分析估计单变量和多变量危险比（HR）和 95%置信区间（CI）。
共纳入 544 例患者，中位生存时间为 11.05 年。52 例（9.6%）LTR 至少发生了 1 例 cSCC，5 年和 10 年后的累积发病率分别为 3.9%和 15.3%。多变量分析显示，硫唑嘌呤和吗替麦考酚酯（MMF）序贯使用，每种药物使用至少 1 年，与仅使用硫唑嘌呤相比，发生 cSCC 的风险较低（风险比[HR]0.24；95%置信区间[CI]0.10 至 0.56）。此外，移植时年龄（HR 3.42；95%CI 1.33 至 8.79）、男性（HR 1.75；95%CI 1.00 至 3.05）、既往皮肤癌（HR 4.75；95%CI 1.14 至 19.76）和吸烟史（HR 3.30；95%CI 1.69 至 6.44）在单变量分析中与发生 cSCC 的风险增加相关。
除了已知的危险因素外，我们发现从硫唑嘌呤转换为 MMF 与 LTR 中 cSCC 发病率的降低有关，这促使我们讨论是否应考虑在高危患者中从硫唑嘌呤转换为 MMF。
