title: Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine.
abstract: OBJECTIVE
  The use of azathioprine and 6-mercaptopurine for inflammatory bowel disease increased in the early 1990s. We sought to determine the effect of this change in therapy on the risk of lymphoma in patients with inflammatory bowel disease.
  
  
  METHODS
  All patients with inflammatory bowel disease at a single tertiary care medical center who developed lymphoma between 1985-2000 were identified and the pathologic features of the lymphoma including presence of Epstein- Barr virus were determined. The patients were divided into two 8-year periods (1985-1992, 1993-2000) corresponding with the introduction of azathioprine and 6-mercaptopurine in 1993.
  
  
  RESULTS
  Eighteen patients with lymphoma were identified, 6 between 1985-1992 and 12 between 1993-2000. Six of 18 lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine, all between 1993-2000. Seven patients developed Epstein-Barr virus-positive lymphoma (1 from 1985-1992, 6 from 1993-2000). Five of 7 Epstein-Barr virus-positive lymphomas occurred in patients treated with azathioprine or 6-mercaptopurine compared with 1 of 11 Epstein-Barr virus-negative lymphomas (P = 0.01). Approximately 1200 patients with inflammatory bowel disease were treated with these agents between 1993-2000.
  
  
  CONCLUSIONS
  Treatment of inflammatory bowel disease with azathioprine or 6-mercaptopurine appears to be associated with a small increased risk of Epstein-Barr virus-positive lymphoma.
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Dayharsh
authors.forename: Edward V
authors.initials: EV
authors.lastname: Loftus
authors.forename: William J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: William J
authors.initials: WJ
authors.lastname: Tremaine
authors.forename: Alan R
authors.initials: AR
authors.lastname: Zinsmeister
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Witzig
authors.forename: William R
authors.initials: WR
authors.lastname: Macon
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Burgart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use*; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology*; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000453:epidemiology; D008223:Lymphoma / Q000453:epidemiology / Q000821:virology*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine