Clinical outcomes of lung transplant recipients with telomerase mutations

https://doi.org/10.1016/j.healun.2015.05.002Get rights and content

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.

Section snippets

Study population

We performed a 5-center retrospective cohort study of 14 lung transplant recipients with telomerase mutations. The subjects were derived from 14 kindreds who underwent lung transplantation between February 21, 2005 and April 5, 2014. Clinical data were obtained by abstracting the medical record. The study was approved by the institutional review board at each of the 5 centers.

Genetic analysis

Genetic sequencing of telomerase genes was available for 11 subjects (78.6%). Of the 3 subjects without genetic testing,

Results

The median age at the time of lung transplant was 60.5 years (interquartile range = 52.0–62.0), 64.3% of subjects were male and most had a family history of pulmonary fibrosis (92.3%) (Table 1). All subjects had radiographic evidence of pulmonary fibrosis before transplant; however, only 42.9% had a radiographic pattern of definite usual interstitial pneumonia on a CT scan of the thorax. The mean follow-up time was 3.2 years (SD ± 2.9) (Table 2). A bilateral lung transplant was performed in 12

Discussion

We describe the clinical outcomes of 14 lung transplant recipients with telomerase mutations in this 5-center retrospective cohort study. After lung transplant, subjects commonly developed bone marrow dyscrasias characterized by leukopenia, anemia, and thrombocytopenia. Infections were common and often recurrent. ACR, when diagnosed, was always minimal in severity. Lung function was acceptable, and the proportion of subjects with CLAD was comparable to the general lung transplant population.20

Disclosure statement

Dr. Tokman’s salary was funded by the National Institutes of Health T32 training grant. The Nina Ireland Program for Lung Health provided funding for statistical analysis.

None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.

The authors thank Dr. Fernando Torres for providing the surveillance and immunosuppressive protocols at University of Texas Southwestern.

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