Crohn’s Disease and Malignant Lymphomas

  • Valerio Zoli
  • Anna Proia
  • Ignazio Majolino
Part of the Updates in Surgery book series (UPDATESSURG)


Crohn’s disease (CD) and ulcerative colitis (UC) are the two major subtypes of inflammatory bowel disease (IBD). Hematological changes, including anemia, hypercoagulable state, thrombocytosis, leukocytosis, and acute or chronic forms of leukemia, have been reported in IBD patients [1]. Patients with IBD are also suspected of being at increased risk of malignant lymphomas, especially non-Hodgkin’s lymphoma (NHL), as of other inflammatory disorders, namely rheumatoid arthritis (RA), Sjögren syndrome, and systemic lupus erythematosus (SLE) [2]. In all these conditions, as in IBD, the respective role of chronic inflammation and of immunosuppressive treatment in the development of lymphomas has not been elucidated, although the role of the immune system in the development of malignant disorders, especially lymphomas, is well recognized.


Systemic Lupus Erythematosus Inflammatory Bowel Disease Ulcerative Colitis Malignant Lymphoma Standardize Incidence Ratio 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Caspi O, Polliack A, Klar R et al (1995) The association of inflammatory bowel disease and leukemia — coincidence or not? Leuk Lymphoma 17:255–262CrossRefPubMedGoogle Scholar
  2. 2.
    Leandro MJ, Isenberg DA (2001) Rheumatic diseases and malignancy — is there an association? Scand J Rheumatol 30:185–188CrossRefPubMedGoogle Scholar
  3. 3.
    Gridley G, Mc Laughlin JK, Ekbom A et al (1993) Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst 85:307–311CrossRefPubMedGoogle Scholar
  4. 4.
    Farrell RJ, Ang Y, Kileen P et al (2000) Increased incidence of non-Hodgkin’s lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low. Gut 47:514–519CrossRefPubMedGoogle Scholar
  5. 5.
    Pearson DC, May GR, Fick GH et al (1995) Azathioprine and 6-mercaptopurine in Crohn disease. A meta-analysis. Ann Intern Med 123:132–142PubMedGoogle Scholar
  6. 6.
    Feagan BG, Fedorak RN, Irvine EJ et al (2000) A comparison of methotrexate with placebo for the maintenance of remission in Crohn’s disease. North American Crohn’s Study Group Investigators. N Engl J Med 342:1627–1632CrossRefPubMedGoogle Scholar
  7. 7.
    Cominelli F (2004) Cytokine-based therapies for crohn’s disease — new paradigms. N Engl J Med 351:2045CrossRefPubMedGoogle Scholar
  8. 8.
    Aithal GP, Mansfield JC (2001) The risk of lymphoma associated with inflammatory bowel disease and immunosuppressive treatment. Aliment Pharmacol Ther 15:1101–1108CrossRefPubMedGoogle Scholar
  9. 9.
    Lewis JD, Bilker WB, Brensinger C et al (2001) Inflammatory bowel disease is not associated with an increased risk of lymphoma. Gastroenterology 121:1080–1088CrossRefPubMedGoogle Scholar
  10. 10.
    Askling J, Brandt L, Lapidus A et al (2005) Risk of haematoepoietic cancer in patients with inflammatory bowel disease. Gut 54:617–622CrossRefPubMedGoogle Scholar
  11. 11.
    Hemmiki K, Li X, Sundquist J et al (2009) Cancer risk in Crohn disease patients. Ann Oncol 20:574–580CrossRefGoogle Scholar
  12. 12.
    Voon Roon AC, Reese G, Teare J et al (2007) The risk of cancer in patients with Crohn’s disease. Dis Colon Rectum 50:839–855CrossRefGoogle Scholar
  13. 13.
    Dayharsh GA, Loftus EV, Sandborn WJ et al (2002) Epstein-Barr virus-positive lymphoma in patients with inflammatory bowel disease treated with azathioprine or 6-mercaptopurine. Gastroenterology 122:72–77CrossRefPubMedGoogle Scholar
  14. 14.
    Wakefield AJ, Fox JD, Sawyerr AM et al (1992) Detection of herpesvirus DNA in the large intestine of patients with ulcerative colitis and Crohn’s disease using the nested polymerase chain reaction. J Med Virol 38:183–190CrossRefPubMedGoogle Scholar
  15. 15.
    Kandiel A, Fraser AG, Korelitz BI et al (2005) Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine. Gut 54:1121–1125CrossRefPubMedGoogle Scholar
  16. 16.
    Lewis JD, Schwartz JS, Lichtenstein GR (2000) Azathioprine for maintenance of remission in Crohn’s disease: benefits outweight the risk of lymphoma. Gastroenterology 118:1018–1024CrossRefPubMedGoogle Scholar
  17. 17.
    Bongartz T, Sutton AJ, Sweeting MJ et al (2006) Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 295:2275–2285CrossRefPubMedGoogle Scholar
  18. 18.
    Kinney T (2003) Immunomodulators and “on demand” therapy with infliximab in Crohn’s disease: clinical experience with 400 infusions. Am J Gastroenterol 98:608–612PubMedGoogle Scholar
  19. 19.
    Colombel JF, Loftus EV Jr, Tremaine WJ et al (2004) The safety profile of infliximab in patients with Crohn’s disease: the Mayo Clinic experience in 500 patients. Gastroenterology 126:19–31CrossRefPubMedGoogle Scholar
  20. 20.
    Ljung T, Karlen P, Schmidt D et al (2004) Infliximab in inflammatory bowel disease: clinical outcome in a population based cohort from Stockholm County. Gut 53:849–853CrossRefPubMedGoogle Scholar
  21. 21.
    Biancone L, Orlando A, Kohn A et al (2006) Infliximab and newly diagnosed neoplasia in Crohn’s disease: a multicentre matched pair study. Gut 55:228–233CrossRefPubMedGoogle Scholar
  22. 22.
    Lichtestein GR, Feagan BG, Cohen RD et al (2006) Serious infections and mortality in association with therapies for Crohn’s disease: TREAT registry. Clin Gastroenterol Hepatol 4:621–630CrossRefGoogle Scholar
  23. 23.
    Siegel CA, Hur C, Korzenik JR et al (2006) Risks and benefits of infliximab for the treatment of Crohn’s disease. Clin Gastroenterol Hepatol 4:1017–1024CrossRefPubMedGoogle Scholar
  24. 24.
    Mittal S, Milner BJ, Johnston PW et al (2006) A case of hepatosplenic gamma-delta T-cell lymphoma with a transient response to fludarabine and alemtuzumab. Eur J Haematol 76:531–534CrossRefPubMedGoogle Scholar
  25. 25.
    Thayu M, Markowitz JE, Mamula P et al (2005) Hepatosplenic T-cell lymphoma in an adolescent patient after immunomodulator and biologic therapy for Crohn’s disease. J Pediatr Gastroenterol Nutr 40:220–222CrossRefPubMedGoogle Scholar
  26. 26.
    Rosh J R, Gross T, Mamula P, Griffiths A, Hyams J. (2007) Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn’s disease: a cautionary tale? Inflamm Bowel Dis 13:1024–1030CrossRefPubMedGoogle Scholar
  27. 27.
    Wöhrer S, Troch M, Zwerina J et al (2007) Influence of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone on serologic parameters and clinical course in lymphoma patients with autoimmune diseases. Ann Oncol 18:647–651CrossRefPubMedGoogle Scholar
  28. 28.
    Michallet AS, Coiffier B (2009) Recent developments in the treatment of aggressive non-Hodgkin lymphoma. Blood Rev 23 (1):11–23CrossRefPubMedGoogle Scholar
  29. 29.
    Maloney D (2008) Allogeneic transplantation following non-myeloablative conditioning for aggressive lymphoma. Bone Marrow Transplant (Suppl 1):535–536Google Scholar
  30. 30.
    Ladetto M, De Marco F, Benedetti F et al (2008) Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in hig-risk follicular lymphoma at diagnosis: the superior disease control of RHDS does not translate into an overall survival advantage. Blood 111:4004–4013CrossRefPubMedGoogle Scholar
  31. 31.
    Fortun PJ & Hawkey CJ. (2008) The role of stem cell transplantation in inflammatory bowel disease. Autoimmunity 41 (8):654–659CrossRefPubMedGoogle Scholar
  32. 32.
    Castro J, Bentch H, Smith L et al (1996) Prolonged clinical remission in patient with inflammatory bowel disease (IBD) after high dose chemotherapy (HDC) and autologous bood stem cell transplantation (ABSCT). Blood 88 (Supplement):133AGoogle Scholar
  33. 33.
    Anumakonda V, Hayee B, Chung-Faye (2007) Remission and relapse of Crohn’s disease following autologous haematopoietic stem cell transplantation for non-Hodgkin’s lymphoma. Gut 56:1325CrossRefPubMedGoogle Scholar
  34. 34.
    Oyama Y, Craig RM, Traynor AR et al (2005) Autologous hematopoietic stem cell transplantation in patients with refractory Crohns disease. Gastroenterology 128:552–563.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2010

Authors and Affiliations

  • Valerio Zoli
    • 1
  • Anna Proia
    • 1
  • Ignazio Majolino
    • 1
  1. 1.Hematology and Stem Cell Transplantation Unit, Institute of Hematotherapy, Department of MedicineSan Camillo-Forlanini HospitalRomeItaly

Personalised recommendations