端粒酶突变的肺移植受者的临床结局
Clinical outcomes of lung transplant recipients with telomerase mutations.
作者信息
Tokman Sofya, Singer Jonathan P, Devine Megan S, Westall Glen P, Aubert John-David, Tamm Michael, Snell Gregory I, Lee Joyce S, Goldberg Hilary J, Kukreja Jasleen, Golden Jeffrey A, Leard Lorriana E, Garcia Christine K, Hays Steven R
机构信息
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco Medical Center, San Francisco, California.
Division of Pulmonary and Critical Care Medicine, University of California, San Francisco Medical Center, San Francisco, California.
出版信息
J Heart Lung Transplant. 2015 Oct;34(10):1318-24. doi: 10.1016/j.healun.2015.05.002. Epub 2015 May 11.
BACKGROUND
Successful lung transplantation for patients with pulmonary fibrosis from telomerase mutations may be limited by systemic complications of telomerase dysfunction, including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes in 14 lung transplant recipients with telomerase mutations.
METHODS
Subjects underwent lung transplantation between February 2005 and April 2014 at 5 transplant centers. Data were abstracted from medical records, focusing on outcomes reflecting post-transplant treatment effects likely to be complicated by telomerase mutations.
RESULTS
The median age of subjects was 60.5 years (interquartile range = 52.0-62.0), 64.3% were male, and the mean post-transplant observation time was 3.2 years (SD ± 2.9). A mutation in telomerase reverse transcriptase was present in 11 subjects, a telomerase RNA component mutation was present in 2 subjects, and an uncharacterized mutation was present in 1 subject. After lung transplantation, 10 subjects were leukopenic and 5 did not tolerate lymphocyte anti-proliferative agents. Six subjects developed recurrent lower respiratory tract infections, 7 developed acute cellular rejection (A1), and 4 developed chronic lung allograft dysfunction. Eight subjects developed at least 1 episode of acute renal failure and 10 developed chronic renal insufficiency. In addition, 3 subjects developed cancer. No subjects had cirrhosis. At data censorship, 13 subjects were alive.
CONCLUSIONS
The clinical course for lung transplant recipients with telomerase mutations is complicated by renal disease, leukopenia with intolerance of lymphocyte anti-proliferative agents, and recurrent lower respiratory tract infections. In contrast, cirrhosis was absent, acute cellular rejection was mild, and development of chronic lung allograft dysfunction was comparable to other lung transplant recipients. Although it poses challenges, lung transplantation may be feasible for patients with pulmonary fibrosis from telomerase mutations.
背景
端粒酶突变所致肺纤维化患者的肺移植成功可能受端粒酶功能障碍的全身并发症限制，包括骨髓抑制、肝硬化和恶性肿瘤。我们描述了14例端粒酶突变肺移植受者的临床结局。
方法
2005年2月至2014年4月期间，5个移植中心的受试者接受了肺移植。数据从医疗记录中提取，重点关注反映可能因端粒酶突变而复杂化的移植后治疗效果的结局。
结果
受试者的中位年龄为60.5岁（四分位间距=52.0-62.0），64.3%为男性，移植后平均观察时间为3.2年（标准差±2.9）。11例受试者存在端粒酶逆转录酶突变，2例存在端粒酶RNA成分突变，1例存在未明确特征的突变。肺移植后，10例受试者出现白细胞减少，5例不耐受淋巴细胞抗增殖剂。6例受试者发生复发性下呼吸道感染，7例发生急性细胞排斥反应（A1级），4例发生慢性移植肺功能障碍。8例受试者至少发生1次急性肾衰竭，10例发生慢性肾功能不全。此外，3例受试者发生癌症。无受试者发生肝硬化。在数据审查时，13例受试者存活。
结论
端粒酶突变的肺移植受者的临床病程因肾脏疾病、白细胞减少伴淋巴细胞抗增殖剂不耐受和复发性下呼吸道感染而复杂化。相比之下，不存在肝硬化，急性细胞排斥反应较轻，慢性移植肺功能障碍的发生与其他肺移植受者相当。尽管存在挑战，但对于端粒酶突变所致肺纤维化患者，肺移植可能是可行的。
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