title: Severe hematologic complications after lung transplantation in patients with telomerase complex mutations.
abstract: 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.
authors.affiliation: APHP, Hôpital Bichat, DHU FIRE Service de Pneumologie A, Centre de compétence des maladies pulmonaires rares, INSERM, Unité 1152, Université Paris Diderot, Paris, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Borie
authors.affiliation: Laboratoire de Génétique, APHP, Hôpital Bichat, Université Paris Diderot, Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kannengiesser
authors.affiliation: Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Hirschi
authors.affiliation: Service de chirurgie thoracique et de transplantation pulmonaire, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Le Pavec
authors.affiliation: Service de Pneumologie B, APHP, Hôpital Bichat, Paris, France.
authors.forename: Hervé
authors.initials: H
authors.lastname: Mal
authors.affiliation: Service de Pneumologie, CHU de Caen, Caen, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bergot
authors.affiliation: Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpital Pontchaillou, IRSET UMR 1085, Université de Rennes 1, Rennes, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Jouneau
authors.affiliation: Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, Hôpital Tenon, Paris, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Naccache
authors.affiliation: INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Paris Descartes-Sorbonne Paris Cité University, Imagine Institute, Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Revy
authors.affiliation: Service d'Immunopathologie clinique, APHP, Hôpital St Louis, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Boutboul
authors.affiliation: Service d'Hématologie greffe, centre de référence maladie rare aplasie médullaire, APHP, Hôpital St Louis, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de la Tour
authors.affiliation: Service de Pneumologie, Centre de compétence des maladies pulmonaires rares, CHRU de Lille, Lille, France.
authors.forename: Lidwine
authors.initials: L
authors.lastname: Wemeau-Stervinou
authors.affiliation: Service de Pneumologie, Centre national de référence des maladies pulmonaires rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Philit
authors.affiliation: Service de Pneumologie, Centre national de référence des maladies pulmonaires rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cordier
authors.affiliation: Service de chirurgie thoracique et de transplantation pulmonaire, Centre Chirurgical Marie Lannelongue, Le Plessis-Robinson, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Thabut
authors.affiliation: APHP, Hôpital Bichat, DHU FIRE Service de Pneumologie A, Centre de compétence des maladies pulmonaires rares, INSERM, Unité 1152, Université Paris Diderot, Paris, France. Electronic address: bruno.crestani@bch.aphp.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Crestani
authors.affiliation: Service de Pneumologie, Centre national de référence des maladies pulmonaires rares, Hôpital Louis Pradel, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
mesh_terms: D000328:Adult; D005260:Female; D006402:Hematologic Diseases / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D019098:Telomerase / Q000235:genetics*
chemical_list: D019098:Telomerase
keywords: familial; genetics; idiopathic pulmonary fibrosis; myelodysplastic syndromes; thrombocytopenia