[en] [en] BACKGROUND: IBD is associated with an increased risk of developing lymphoma. Although recent data clarifies lymphoma epidemiology in IBD patients, clinical and pathological characteristics of lymphoma occurring in IBD remain ill-known.
METHODS: Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif (GETAID) and the Lymphoma Study Association (LYSA). We characterized clinical and prognostic features for the 3 most frequent lymphoma subtypes occurring in IBD. We performed a multicentric case-control study. Controls (lymphoma de novo) were matched (5:1) to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, IPI/FLIPI indexes. Overall survival (OS) and progression free survival were compared between cases and controls.
RESULTS: 133 IBD patients with lymphoma were included (males = 62.4 %, median age at lymphoma diagnosis = 49 years in males ; 42 in females). Most had Crohn's disease (73.7 %) and were exposed to thiopurines (59.4 %). The most frequent lymphoma subtypes were diffuse large B cell lymphoma (DLBCL, 45.1 %), Hodgkin lymphoma (HL, 18.8 %), and follicular lymphoma (FL, 10.5 %). When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls (p = 0.0064, hazard ratio = 0.36) or similar (HL and FL).
CONCLUSION: Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the scarcity of this situation, those patients should be managed in expert centers.
Disciplines :
Gastroenterology & hepatology
Author, co-author :
Muller, Marie ; Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France
Broséus, Julien; University of Lorraine, Inserm U1256 « Nutrition - Genetics and exposure to environmental risks - NGERE », F-54000, Nancy, France ; University of Lorraine, CHRU-Nancy Hematology Laboratory, Laboratory department, F-54000 Nancy, France
Guilloteau, Adrien; Registre des hemopathies Malignes de Côte d'Or, Inserm U1231, University of Burgundy and Dijon University Hospital, Dijon, France
Wasse, Stéphane; Registre des hemopathies Malignes de Côte d'Or, Inserm U1231, University of Burgundy and Dijon University Hospital, Dijon, France
Thiéblemont, Catherine; AP-HP, Saint-Louis Hospital, Hemato-oncology, University of Paris, Paris, France
Nancey, Stéphane; Department of Gastroenterology, University Claude Bernard Lyon 1, Hospices Civils de Lyon, CHU Lyon-Sud, Lyon, France
Cadiot, Guillaume; Department of Hepato-Gastro-Enterology, Reims University Hospital, France
Amiot, Aurélien; Department of Gastroenterology, Henri Mondor University Hospital, AP-HP, Paris Est Créteil University, Créteil, France
Laharie, David; Department of Hepato-Gastro-Enterology, Bordeaux University Hospital, Pessac, France
Vieujean, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de gastroentérologie, hépatologie, onco. digestive
Bouhnik, Yoram; Institut National de la Santé et Recherche Médicale et Université Paris Diderot, Paris Hôpital Beaujon, AP-HP, Paris, France
Martineau, Chloé; Department of Gastroenterology, Hôpital Européen George Pompidou, AP-HP, Paris, France
Michiels, Christophe; Department of Hepato-Gastro-Enterology, Dijon University Hospital, France
Hebuterne, Xavier; Department of Hepato-Gastro-Enterology, Nice University Hospital, France
Savoye, Guillaume; Department of Hepato-Gastro-Enterology, Rouen University Hospital, France
Franchimont, Denis; Department of Hepato-Gastro-Enterology, Erasme University Hospital, Brussels, Belgium
Seksik, Philippe; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Department of Gastroenterology, F75012, Paris, France
Beaugerie, Laurent; Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Department of Gastroenterology, F75012, Paris, France
Maynadié, Marc; Registre des hemopathies Malignes de Côte d'Or, Inserm U1231, University of Burgundy and Dijon University Hospital, Dijon, France
Feugier, Pierre; University of Lorraine, Inserm U1256 « Nutrition - Genetics and exposure to environmental risks - NGERE », F-54000, Nancy, France ; Department of Clinical Hematology, Nancy University Hospital, University of Lorraine, Nancy, France
Peyrin-Biroulet, Laurent; Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Nancy, France ; University of Lorraine, Inserm U1256 « Nutrition - Genetics and exposure to environmental risks - NGERE », F-54000, Nancy, France
Weinstock DM. Epstein–Barr virus, lymphoma risk and the potential role of HIV infection in IBD patients undergoing immunosuppression. Dig Dis 2010;28:519–24. doi:10.1159/000320411
Molodecky NA, Soon IS, Rabi DM, et al. Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 2012;142:46–54.e42; quiz e30. doi:10.1053/j.gastro.2011.10.001
Beaugerie L, Brousse N, Bouvier AM, et al; CESAME Study Group. Lymphoproliferative disorders in patients receiving thiopurines for inflammatory bowel disease: a prospective observational cohort study. Lancet 2009;374:1617–25. doi:10.1016/S0140-6736(09)61302-7
Loftus EV, Tremaine WJ, Habermann TM, Harmsen WS, Zinsmeister AR, Sandborn WJ. Risk of lymphoma in inflammatory bowel disease. Am J Gastroenterol 2000;95:2308–12. doi:10.1111/ j.1572-0241.2000.02316.x
Afif W, Sandborn WJ, Faubion WA, et al. Risk factors for lymphoma in patients with inflammatory bowel disease: a case-control study. Inflamm Bowel Dis 2013;19:1384–9. doi:10.1097/ MIB.0b013e318281325e
Muller M, Broséus J, Feugier P, et al. Characteristics of lymphoma in patients with inflammatory bowel disease: a systematic review. J Crohns Colitis 2021;15:827–39. doi:10.1093/ecco-jcc/jjaa193
Sokol H, Beaugerie L, Maynadié M, et al. Excess primary intestinal lymphoproliferative disorders in patients with inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2063–71. doi:10.1002/ ibd.22889
Khan N, Abbas AM, Lichtenstein GR, Loftus EV, Bazzano LA. Risk of lymphoma in patients with ulcerative colitis treated with thiopurines: a nationwide retrospective cohort study. Gastroenterology 2013;145:1007–1015.e3. doi:10.1053/j.gastro.2013.07.035
Kotlyar DS, Lewis JD, Beaugerie L, et al. Risk of lymphoma in patients with inflammatory bowel disease treated with azathioprine and 6-mercaptopurine: a meta-analysis. Clin Gastroenterol Hepatol 2015;13:847–58.e4; quiz e48. doi:10.1016/j.cgh.2014.05.015
Muller M, D’Amico F, Bonovas S, Danese S, Peyrin-Biroulet L. TNF inhibitors and risk of malignancy in patients with inflammatory bowel diseases: a systematic review. J Crohns Colitis 2020;15:840–59. doi:10.1093/ecco-jcc/jjaa186
Dayharsh GA, Loftus EV, Sandborn WJ, et al. Epstein-Barr virus–positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology 2002;122:72–7. doi:10.1053/gast.2002.30328
Lemaitre M, Kirchgesner J, Rudnichi A, et al. Association between use of thiopurines or tumor necrosis factor antagonists alone or in combination and risk of lymphoma in patients with inflammatory bowel disease. JAMA 2017;318:1679–86. doi:10.1001/ jama.2017.16071
Chupin A, Perduca V, Meyer A, Bellanger C, Carbonnel F, Dong C. Systematic review with meta-analysis: comparative risk of lymphoma with anti-tumour necrosis factor agents and/or thiopurines in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2020;52:1289–97. doi:10.1111/apt.16050
Peyrin-Biroulet L, Rahier J-F, Kirchgesner J, et al. I-CARE, a European prospective cohort study assessing safety and effectiveness of biologics in inflammatory bowel disease. Clin Gastroenterol Hepatol 2022:S1542356522009168. doi:10.1016/j. cgh.2022.09.018
Severyns T, Kirchgesner J, Lambert J, et al. Prognosis of lymphoma in patients with known inflammatory bowel disease: a French multicentre cohort study. J Crohns Colitis 2020;14:1222–30. doi:10.1093/ecco-jcc/jjaa048
Hennessy S, Bilker WB, Berlin JA, Strom BL. Factors influencing the optimal control-to-case ratio in matched case-control studies. Am J Epidemiol 1999;149:195–7. doi:10.1093/oxfordjournals.aje. a009786
Woodward M. Epidemiology: Study Design and Data Analysis, Third Edition. 0 ed. New York: Chapman and Hall/CRC; 2013.
Le Guyader-Peyrou S, Belot A, Maynadié M, et al. Cancer incidence in France over the 1980–2012 period: hematological malignancies. Revue Épidémiol Santé Publique 2016;64:103–12. doi:10.1016/j. respe.2015.12.017