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Risk of malignant lymphoma in patients with inflammatory bowel diseases: A Dutch nationwide study

Vos, A. C.W. MSc1; Bakkal, N. MSc1; Minnee, R. C. MD, PhD2; Casparie, M. K. MD3; de Jong, D. J. MD, PhD4; Dijkstra, G. MD, PhD5; Stokkers, P. MD, PhD2; van Bodegraven, A. A. MD, PhD6; Pierik, M. MD, PhD7; van der Woude, C. J. MD, PhD8; Oldenburg, B. MD, PhD9; Hommes, D. W. MD, PhD1*for the Initiative on Crohn's and Colitis (ICC)

doi: 10.1002/ibd.21582
Original Clinical Articles

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. (Inflamm Bowel Dis 2011;)

1 Department of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden, Netherlands

2 Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

3 Foundation PALGA, Utrecht, Netherlands

4 Department of Gastroenterology, Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

5 Department of Gastroenterology and Hepatology, University Medical Center Groningen, Groningen, Netherlands

6 Department of Gastroenterology and Hepatology, VU University Medical Center, Amsterdam, Netherlands

7 Department of Gastroenterology, University Hospital Maastricht, Maastricht, Netherlands

8 Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, Netherlands

9 Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands

*Reprints: Leiden University Medical Center, Department of Gasteroenterology and Hepatology, C4-P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands


Received 18 August 2010; Accepted 20 October 2010

Published online 22 December 2010 in Wiley Online Library (

Grant sponsor: Netherlands Society of Gastroenterology.

Supported by a grant from the Gastrostart Fund of the Netherlands Society of Gastroenterology (Project 2005-14).

© Crohn's & Colitis Foundation of America, Inc.
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