Clinical outcomes of lung transplant recipients with 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.
References (30)
- et al.
Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome
Blood
(2003) - et al.
Short telomeres: from dyskeratosis congenita to sporadic aplastic anemia and malignancy
Transl Res
(2013) - et al.
Voriconazole prophylaxis in lung transplant recipients
Am J Transplant
(2006) - et al.
Revision of the 1996 working formulation for the standardization of nomenclature in the diagnosis of lung rejection
J Heart Lung Transplant
(2007) - et al.
Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation
J Heart Lung Transplant
(2005) - et al.
A new classification system for chronic lung allograft dysfunction
J Heart Lung Transplant
(2014) - et al.
The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Lung and Heart-Lung Transplant Report—2011
J Heart Lung Transplant
(2011) - et al.
The Registry of the International Society for Heart and Lung Transplantation: 29th Adult Lung and Heart-Lung Transplant Report—2012
J Heart Lung Transplant
(2012) - et al.
Association between telomere length in blood and mortality in people aged 60 years or older
Lancet
(2003) - et al.
Bronchiolitis obliterans syndrome: the final frontier for lung transplantation
Chest
(2011)
Cytokine gene expression in rejecting and tolerant rat lung allograft models: analysis by RT-PCR
Transpl Immunol
Risk of hematologic toxicities in patients with solid tumors treated with everolimus: a systematic review and meta-analysis
Crit Rev Oncol Hematol
Pulmonary fibrosis: patterns and perpetrators
J Clin Invest
Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations
PLoS One
Telomere diseases
N Engl J Med
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