Review article: the risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment

Abstract

Lymphoma complicating inflammatory bowel disease is well described. Whether the risk of lymphoma is incre‐ ased by immunosuppressive treatment with azathiop‐ rine, 6‐mercaptopurine or infliximab is a common concern among patients and physicians considering using these agents. This review aims to quantify the lymphoma risk in inflammatory bowel disease and the added risk attributable to these treatments. The evidence from published cases is that lymphomas occur at sites of active inflammatory bowel disease more often than expected for this to be a chance association. Studies on inflammatory bowel disease populations are conflicting, with some follow‐up studies from large inflammatory bowel disease clinics showing an increase in lymphoma incidence, while other population‐based studies show little or no increase in risk of lymphoma. A small increase in lymphoma risk in inflammatory bowel disease, perhaps 2–3‐fold, may be compatible with both sets of data. Studies of the risks associated with immuno‐ suppression are less satisfactory, with smaller numbers of patients and relatively short follow‐up. The available evidence would support a further increase in lymphoma risk associated with immunosuppressive treatment in inflammatory bowel disease of around fivefold compared to no immunosuppressive use, and tenfold compared to the general population. The risks appear to be less than that associated with renal and hepatic transplant‐related immunosuppression. Infliximab treatment is still too new to make a full assessment of its long‐term safety, but post‐marketing surveillance currently suggests that lymphoma risk may not be any greater than that associated with azathioprine and 6‐mercaptopurine. Population‐wide surveillance for lymphoma in inflammatory bowel disease would be required to narrow the confidence intervals on these estimates of lymphoma risk in inflammatory bowel disease and immunosuppressive treatment.

Lymphoma Rates Are Low but Increased in Patients With Psoriasis

“…These results are important in that they add psoriasis to the literature linking chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease to lymphoma. 40,41 As novel immunosuppressive treatments are increasingly used in patients with psoriasis, it will be important to understand baseline rates of lymphoma in this population to determine if these treatments further increase the risk of lymphoproliferative diseases. For example, the results of this study and others 9,22 suggest that it may be inappropriate to compare the rate of lymphoma in patients with psoriasis who are treated with a novel therapy with lymphoma rates found in the general population, as the baseline rate of lymphoproliferative diseases is greater in the former than in the latter.…”

Ionizing radiation in patients with Crohn’s disease: Estimation and associated factors

“…Chronic inflammation of the gastrointestinal tract in patients with CD entails a greater risk of developing colorectal cancer, small bowel cancer and lymphoma (11). In addition, the use of immunosuppressive drugs such as azathioprine and mercaptopurine, and monoclonal antibodies such as infliximab, could increase the risk of malignancy (8,11,12). On the other hand, thiopurines cause an increase in this risk by enhancing radiosensitivity (13).…”

Primäres ZNS-Lymphom während der Behandlung von Autoimmunerkrankungen mit Azathioprin

“…Darüber hinaus bedingt die interindividuell unterschiedliche, genetisch determinierte, enzymatische Metabolisierung von Azathioprin und dessen Metabolite eine interindividuell unterschiedliche Toxizität und Karzinogenität für Azathioprin [6,9,19,41]. Neben bösartigen Neubildungen der Haut, des Gebärmutterhalses und der Vulva sind vor allem Lymphome, insbesondere Non-Hodgkin-Lymphome (NHL), in der Literatur beschrieben [1,5,10,12,19,21,24,29,35,41,43].…”

“…Die durch Azathioprin induzierte Immunsuppression kann in einen ursäch-lichen Zusammenhang mit der Entwicklung des PZNSL gebracht werden [1,21,23]. Angesichts des kurzen Behandlungszeitraum von lediglich 9 Monaten mit Azathioprin [24,28,34,45] müssen neben Azathioprin auch weitere, möglicherwei-se additive, immunsuppressive Faktoren für die Entwicklung des PZNSL im aktuellen Fall diskutiert werden.…”