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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.
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