title: Chronic immune stimulation might act as a trigger for the development of acute myeloid leukemia or myelodysplastic syndromes.
abstract: OBJECTIVE
  Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) often present with infections, but there are little data to assess whether a personal history of selected infections may act as pathogenic triggers. To additionally expand our knowledge on the role of immune stimulation in the causation of AML and MDS, we have conducted a large, population-based study to evaluate the risk of AML and MDS associated with a prior history of a broad range of infections or autoimmune diseases.
  
  
  METHODS
  By using population-based central registries in Sweden, we included 9,219 patients with AML, 1,662 patients with MDS, and 42,878 matched controls. We used logistic regression to calculate odds ratios (ORs) and 95% CIs for the association of AML or MDS with infectious and/or autoimmune diseases.
  
  
  RESULTS
  Overall, a history of any infectious disease was associated with a significantly increased risk of both AML (OR, 1.3; 95% CI, 1.2 to 1.4) and MDS (OR, 1.3; 95% CI, 1.1 to 1.5). These associations were significant even when we limited infections to those occurring 3 or more years before AML/MDS. A previous history of any autoimmune disease was associated with a 1.7-fold (95% CI, 1.5 to 1.9) increased risk for AML and 2.1-fold (95% CI, 1.7 to 2.6) increased risk for MDS. A large range of conditions were each significantly associated with AML and MDS.
  
  
  CONCLUSIONS
  Our novel findings indicate that chronic immune stimulation acts as a trigger for AML/MDS development. The underlying mechanisms may also be due to a common genetic predisposition or an effect of treatment for infections/autoimmune conditions.
authors.affiliation: Dept of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. sigurdur.kristinsson@karolinska.se
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Malin
authors.initials: M
authors.lastname: Hultcrantz
authors.forename: Åsa R
authors.initials: ÅR
authors.lastname: Derolf
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
authors.forename: Lynn R
authors.initials: LR
authors.lastname: Goldin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001327:Autoimmune Diseases / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D016022:Case-Control Studies; D003141:Communicable Diseases / Q000150:complications / Q000453:epidemiology / Q000276:immunology*; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000276:immunology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology / Q000276:immunology*; D016017:Odds Ratio; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D013997:Time Factors