Hepatosplenic T-cell lymphoma in patients receiving TNF-α inhibitor therapy: expanding the groups at risk

Eur J Gastroenterol Hepatol. 2011 Nov;23(12):1150-6. doi: 10.1097/MEG.0b013e32834bb90a.


Background: Hepatosplenic T-cell lymphoma (HSTCL) is a rare, lethal disease generally seen in young male patients with inflammatory bowel disease. The study of biologic and immunomodulator naive patients in Crohn's disease (SONIC), advocates combining infliximab with an immunomodulator in moderate-to-severe Crohn's disease. Unfortunately, combined immunosuppression increases risk for HSTCL. We herein review all cases of HSTCL reported to the Food and Drug Administration (FDA) in patients receiving TNF-α inhibitors.

Methods: Individual reports from the FDA Adverse Event Reporting System database for lymphomas from the biological agents - infliximab, adalimumab, certolizumab, natalizumab, and etanercept were downloaded and analyzed with Microsoft Access. Full reports for all identified HSTCL cases were obtained from the FDA.

Results: Twenty-five cases of HSTCL were identified. Twenty-two (88%) patients had inflammatory bowel disease and three had rheumatoid arthritis. Four cases (16%) were in women and four patients were above 65 years of age. Twenty-four cases (96%) also received an immunomodulator (azathioprine, 6-mercaptopurine, or methotrexate). Two patients received adalimumab alone.

Conclusion: HSTCL is no longer restricted to the previously identified risk group of young male patients, but can also occur in patients with rheumatoid arthritis, females and older adults receiving TNF-α inhibitors and immunomodulators. Improved disease outcomes using combination therapy should be tempered by the risk of developing HSTCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Adverse Drug Reaction Reporting Systems
  • Aged
  • Arthritis, Rheumatoid / drug therapy
  • Biological Products / adverse effects*
  • Biological Products / therapeutic use
  • Child
  • Drug Therapy, Combination
  • Female
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use
  • Inflammatory Bowel Diseases / drug therapy
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / epidemiology
  • Lymphoma, T-Cell / chemically induced*
  • Lymphoma, T-Cell / epidemiology
  • Male
  • Middle Aged
  • Splenic Neoplasms / chemically induced*
  • Splenic Neoplasms / epidemiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • United States / epidemiology
  • Young Adult


  • Biological Products
  • Immunosuppressive Agents
  • Tumor Necrosis Factor-alpha