title: Increased risk of acute myeloid leukemias and myelodysplastic syndromes in patients who received thiopurine treatment for inflammatory bowel disease.
abstract: OBJECTIVE
  Treatment with immunosuppressive thiopurines such as azathioprine is associated with an increased risk of leukemogenesis. We assessed the risk of myeloid disorders, such as acute myeloid leukemia and myelodysplastic syndromes, in a large cohort of patients with inflammatory bowel disease (IBD) in France.
  
  
  METHODS
  We performed a prospective observational study of 19,486 patients with IBD enrolled in the Cancers Et Surrisque Associé aux Maladies inflammatoires intestinales En France (CESAME) study from May 2004 through June 2005; patients were followed through December 31, 2007. The incidence of myeloid disorders in the general population, which was used for reference, was determined from the French Network of Cancer Registries.
  
  
  RESULTS
  During 49,736 patient-years of follow-up, 5 patients were diagnosed with incident myeloid disorders (2 with acute myeloid leukemia and 3 with myelodysplastic syndromes). Four of these patients had been exposed to thiopurines (1 with ongoing treatment and 3 with past exposure). The risk of myeloid disorders was not increased among the overall IBD population, compared with the general population; the standardized incidence ratio (SIR) was 1.80 (95% confidence interval [CI], 0.58-4.20). The risk of myeloid disorders was not increased among patients with IBD and ongoing thiopurine treatment (SIR, 1.54; 95% CI, 0.05-8.54), but patients with past exposures to thiopurines had an increased risk of myeloid disorders (SIR, 6.98; 95% CI, 1.44-20.36).
  
  
  CONCLUSIONS
  Past exposure to thiopurines increases the risk of myeloid disorders 7-fold among patients with IBD. This finding should be considered when initiating thiopurine therapy, so risks and benefits can be calculated.
authors.affiliation: Unité U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.
authors.forename: Anthony
authors.initials: A
authors.lastname: Lopez
authors.affiliation: Registre des Hémopathies Malignes de Côte d'Or, EA 4184, Faculté de Médecine, Dijon, France.
authors.forename: Morgane
authors.initials: M
authors.lastname: Mounier
authors.affiliation: CHU Dijon, Registre Bourguignon des Cancers Digestifs, INSERM Unité 866, Université de Bourgogne, Dijon, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Bouvier
authors.affiliation: Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine F-75012 and ERL 1057 INSERM/UMRS 7203, UPMC University of Paris 06F-75005, Paris, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Carrat
authors.affiliation: Registre des Hémopathies Malignes de Côte d'Or, EA 4184, Faculté de Médecine, Dijon, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadié
authors.affiliation: Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine F-75012 and ERL 1057 INSERM/UMRS 7203, UPMC University of Paris 06F-75005, Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Beaugerie
authors.affiliation: Unité U954 and Department of Gastroenterology, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France. Electronic address: peyrinbiroulet@gmail.com.
authors.forename: Laurent
authors.initials: L
authors.lastname: Peyrin-Biroulet
mesh_terms: D000293:Adolescent; D000328:Adult; D001379:Azathioprine / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015994:Incidence; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000453:epidemiology*; D011446:Prospective Studies; D018570:Risk Assessment; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: CESAME; Cancer Risk; Crohn’s Disease; Immune Suppression; Myelodysplastic Syndrome; Ulcerative Colitis