title: Hepatosplenic T-cell lymphoma in patients receiving TNF-α inhibitor therapy:  expanding the groups at risk.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, Research Institute, NorthShore University HealthSystem, Evanston, Illinois, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Parakkal
authors.forename: Humberto
authors.initials: H
authors.lastname: Sifuentes
authors.forename: Rumi
authors.initials: R
authors.lastname: Semer
authors.forename: Eli Daniel
authors.initials: ED
authors.lastname: Ehrenpreis
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D001688:Biological Products / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D016399:Lymphoma, T-Cell / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D013160:Splenic Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001688:Biological Products; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha