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Gut. 2002 August; 51(2): 296.
PMCID: PMC1773319

Immunosuppression, IBD, and risk of lymphoma

We read with interest the two recent reports of lymphoma in patients with inflammatory bowel disease (IBD) (Farrell et al,Gut 2000;47:514–19 and Palli et al, Gastroenterology 2000;119:647–53). We believe the report from Farrell of four cases of lymphoma in a cohort of 782 patients (of whom 238 had received immunosuppression) considerably overestimates the relative risk of lymphoma in IBD patients. They calculate a relative risk of lymphoma as 31 for the whole cohort and 59 for the group treated with immunosuppressives (compared with the general population).

Immunosuppressive therapy is well recognised as increasing the risk of developing non-Hodgkin's lymphoma (NHL) in organ transplant patients.1 The risk of NHL is increased in other inflammatory conditions, such as rheumatoid arthritis2 and psoriasis, although how much is attributable to the underlying disease and how much is due to the drug is unclear.

For IBD, if the incidence of lymphoma is indeed increased, is this due to drug or disease? Two recent reviews3,4 have examined this question in detail.

Several large well designed population based studies have been performed specifically to examine the baseline risk of lymphoma in IBD. In none of these studies does the relative risk for NHL significantly exceed one, while only one study (Palli et al) has shown an excess risk of Hodgkin's disease (relative risk 9.3; 95% confidence interval 2.5–23.8).

A number of smaller case series have been published which show an increased incidence of NHL. This type of study, although interesting, should not be regarded as evidence of increased risk as case ascertainment bias is likely to exist.

Several studies have specifically addressed the question of immunosuppression in IBD. In total, only 11 cases of lymphoma were described in more than 4000 patients who had received immunotherapy, with over 17 000 patient years of follow up. Extrapolating these data to lymphoma rates in the general population may be unreliable, particularly as lymphoma rates vary widely geographically, by sex and age.5

We believe that compared with the other known risks of immunosuppression, such as myelosuppression and infection, the risk of developing lymphoma (if it does exist) is likely to be of minor clinical significance and to be outweighed by the potential benefit of these treatments in patients with IBD.6


1. Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993;342:1514–16. [PubMed]
2. Kinlen LJ. Incidence of cancer in rheumatoid arthritis and other disorders after immunosuppressive treatment. Am J Med 1985;78:44–9.
3. Aithal GP, Mansfield JC. Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment. Aliment Pharmacol Ther 2001;15:1101–8. [PubMed]
4. Bebb JR, Logan RPH. Review article: Does the use of immunosuppressive therapy in IBD increase the subsequent risk of developing lymphoma? Aliment Pharmacol Ther 2001;15:1843–9. [PubMed]
5. Cancer incidence in five continents, vol. 5. IARC Scientific Publications No 88. Oxford: Oxford University Press, 1987.
6. Lewis JD, Schwartz JS, Lichtenstein GR. Azathioprine for maintenance of remission in Crohn's disease: Benefits outweigh the risk of lymphoma. Gastroenterology 2000;118:1018–1024. [PubMed]

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