title: Risk of malignant lymphoma in patients with inflammatory bowel diseases: a Dutch nationwide study.
abstract: BACKGROUND
  Immune suppressant medications such as thiopurines and anti-tumor necrosis factor agents are important for maintaining disease control in most patients with inflammatory bowel diseases (IBDs); however, their use has been associated with the development of malignant lymphoma. The purpose of this Dutch nationwide study was to estimate the relative risk of malignant lymphoma in IBD patients.
  
  
  METHODS
  IBD patients who developed a lymphoma between 1997 and 2004 were identified using the Dutch National Database of PALGA. Data from confirmed cases were collected from individual hospitals, including data on Epstein-Barr virus (EBV). The age-adjusted 8-year incidence of malignant lymphoma in the Netherlands was retrieved from the Central Bureau of Statistics.
  
  
  RESULTS
  Forty-two hospitals were visited and 285 matches evaluated in the total cohort of 17,834 IBD patients. Forty-four lymphomas were observed, resulting in a relative risk of 1.27 (95% confidence interval [CI]: 0.92-1.68). Only 19 of 44 patients (43%) were exposed to azathioprine/6-mercaptopurine (AZA/6-MP). Remarkably, 92% of patients (11/12) with EBV-positive lymphoma used AZA/6-MP, in contrast to only 19% patients (4/21) with EBV-negative lymphoma, suggesting a strong relation between EBV-positive lymphoma and thiopurine use.
  
  
  CONCLUSIONS
  This nationwide study does not suggest a significant overall increased risk for lymphoma in IBD patients. A distinct correlation between EBV-positive lymphoma and AZA/6-MP use was observed.
authors.affiliation: Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands.
authors.forename: A C W
authors.initials: AC
authors.lastname: Vos
authors.forename: N
authors.initials: N
authors.lastname: Bakkal
authors.forename: R C
authors.initials: RC
authors.lastname: Minnee
authors.forename: M K
authors.initials: MK
authors.lastname: Casparie
authors.forename: D J
authors.initials: DJ
authors.lastname: de Jong
authors.forename: G
authors.initials: G
authors.lastname: Dijkstra
authors.forename: P
authors.initials: P
authors.lastname: Stokkers
authors.forename: A A
authors.initials: AA
authors.lastname: van Bodegraven
authors.forename: M
authors.initials: M
authors.lastname: Pierik
authors.forename: C J
authors.initials: CJ
authors.lastname: van der Woude
authors.forename: B
authors.initials: B
authors.lastname: Oldenburg
authors.forename: D W
authors.initials: DW
authors.lastname: Hommes
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000009:adverse effects*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D004854:Herpesvirus 4, Human / Q000472:pathogenicity; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D008223:Lymphoma / Q000139:chemically induced* / Q000453:epidemiology / Q000821:virology; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine