title: Incidence, presentation, and prognosis of malignancies in ataxia-telangiectasia: a report from the French national registry of primary immune deficiencies.
abstract: OBJECTIVE
  Biallelic mutations in ATM cause ataxia-telangiectasia (AT), a rare inherited disease with a high incidence of cancer. Precise estimates of the risk, presentation, and outcomes of cancer in patients with AT need to be addressed in large series.
  
  
  METHODS
  In this large retrospective cohort, 69 patients with cancers (24.5%) were identified among 279 patients with AT. Centralized review was performed on 60% of the lymphomas. Incidence rates were compared with the French population, and risk factors were analyzed.
  
  
  RESULTS
  Eight patients developed acute leukemias (including four T-cell acute lymphoblastic leukemias), 12 developed Hodgkin lymphoma (HL), 38 developed non-Hodgkin lymphoma (NHL), three developed T-cell prolymphocytic leukemia (T-PLL), and eight developed carcinoma at a median age of 8.3, 10.6, 9.7, 24.2, and 31.4 years, respectively (P < .001). The majority of NHLs were aggressive B-cell NHL. Epstein-Barr virus was associated with all of the HLs and 50% of the NHLs. Overall survival was shorter in patients with AT who developed cancer compared with those who did not develop cancer (15 v 24 years, respectively; P < .001). Survival was improved in patients who achieved a major response to treatment (3.46 v 0.87 years for major v minor responses, respectively; P = .011). Immunodeficiency was associated with increased risk of cancer. ATM mutation type was associated with a difference in survival in the entire cohort but not with cancer incidence or cancer survival.
  
  
  CONCLUSIONS
  B-cell NHL, HL, and acute lymphoblastic leukemia occur at a high rate and earlier age than carcinomas in AT. T-PLLs are rarer than initially reported. Prognosis is poor, but patients may benefit from treatment with an improved survival.
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France. felipe.suarez@nck.aphp.fr.
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Nizar
authors.initials: N
authors.lastname: Mahlaoui
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Danielle
authors.initials: D
authors.lastname: Canioni
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Andriamanga
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Dubois d'Enghien
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Brousse
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Jais
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.affiliation: Felipe Suarez, Nizar Mahlaoui, Danielle Canioni, Nicole Brousse, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Hôpital Universitaire Necker-Enfants Malades, Assistance Publique-Hôpitaux de Paris; Felipe Suarez, Nizar Mahlaoui, Chantal Andriamanga, Alain Fischer, and Olivier Hermine, French National Reference Center for Primary Immune Deficiency; Felipe Suarez, Nizar Mahlaoui, Jean-Philippe Jais, Alain Fischer, and Olivier Hermine, Imagine Institute, Institut National de la Recherche Scientifique Unité Mixte de Recherche 1163, Sorbonne Paris Cité, Université Paris Descartes; Felipe Suarez and Olivier Hermine, Centre National de la Recherche Scientifique Equipe de Recherche Labellisée 8254; Danielle Canioni, Nicole Brousse, and Dominique Stoppa-Lyonnet, Université Paris Descartes; Catherine Dubois d'Enghien and Dominique Stoppa-Lyonnet, Institut Curie; and Alain Fischer, Collège de France, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Stoppa-Lyonnet
mesh_terms: D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D001260:Ataxia Telangiectasia / Q000150:complications* / Q000401:mortality*; D005260:Female; D005602:France / Q000453:epidemiology; D006689:Hodgkin Disease / Q000453:epidemiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes; D015994:Incidence; D007938:Leukemia / Q000453:epidemiology*; D008223:Lymphoma / Q000453:epidemiology*; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis* / Q000453:epidemiology* / Q000235:genetics / Q000401:mortality / Q000628:therapy; D011379:Prognosis; D012042:Registries; D012189:Retrospective Studies