Severe hematologic complications after lung transplantation in patients with telomerase complex mutations

https://doi.org/10.1016/j.healun.2014.11.010Get rights and content

Background

Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations.

Methods

Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases.

Results

There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35–61 years) at diagnosis and 52 years (range, 37–62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59–1,709 days).

Conclusions

Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.

Section snippets

Patients

In this retrospective, observational, non-interventional study, all 10 French lung transplant centers were contacted to identify patients with TERT or TR mutations referred for lung transplantation during the period from 2009 to 2013; the genetics laboratory began to perform sequencing of these genes in 2009. In addition, cases were cross-identified through the only genetic laboratory in France that centrally assesses for telomerase mutations and by the Groupe dʼEtudes et de Recherche sur les

Clinical characteristics at diagnosis of PF

From January 2009 to October 2013, 9 patients with TERT or TR mutations received lung transplants in France. The main clinical characteristics of the patients at diagnosis are shown in Table 1. Interstitial lung disease was diagnosed as IPF in 7 patients, pneumoconiosis in 1 patient, and chronic hypersensitivity pneumonitis in 1 patient. In 6 patients, there was some degree of exposure to inhaled contaminants (Table 1). Extrapulmonary manifestations suggestive of telomere syndrome were present

Discussion

The present study is the largest report on outcomes of lung transplantation in a comprehensive series of patients with TERT or TR mutations. The main finding of this study is that hematologic complications following lung transplantation were more frequent in this patient population than in a control group of lung transplant recipients for PF, with possible sepsis related to bone marrow failure, warranting close attention of clinicians in the pre-transplant evaluation and in the post-transplant

Disclosure statement

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. This work was supported by the Chancellerie des Universités de Paris (legs Poix) and by a grant “FPI-SPC” from Université Sorbonne Paris Cité.

The authors thank the following individuals: Elodie Lainey, Thierry Leblanc, Gaelle Dauriat, Olivier Brugière, Anne-Cécile Métivier, Bernard Grandchamp, Peter Dorfmuller,

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    These authors have contributed equally to this work.

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