Original article—alimentary tract
A Systematic Review of Factors That Contribute to Hepatosplenic T-Cell Lymphoma in Patients With Inflammatory Bowel Disease

https://doi.org/10.1016/j.cgh.2010.09.016Get rights and content

Background & Aims

Hepatosplenic T-cell lymphoma (HSTCL) is a rare and usually fatal lymphoma that primarily affects men younger than 35 years old. Treatment of patients with inflammatory bowel disease (IBD) using antibodies to tumor necrosis factor (anti-TNFs) and thiopurines has been associated with HSTCL. We investigated the medications, duration of therapy, and ages of patients associated with HSTCL.

Methods

We collected and analyzed data on the association between HSTCL, and anti-TNF and thiopurine therapies in patients with IBD from published reports and the MedWatch reporting system of the US Food and Drug Administration.

Results

Of 36 patients with HSTCL, 20 received therapy with infliximab and a thiopurine and 16 received a thiopurine as monotherapy for IBD. Four patients who had been treated with infliximab and a thiopurine also received adalimumab. One of these patients had been given infliximab, adalimumab, and natalizumab. Of 31 patients of known gender, only 2 were female. Twenty-seven of the 30 patients of known age were younger than 35 years old.

Conclusions

Most patients with HSTCL who received long-term therapy (at least 2 y) with thiopurines for IBD were men younger than 35 years old. There were no reported cases of HSTCL in patients with IBD who received only anti-TNF therapy. Physicians should consider giving thiopurines and anti-TNF agents to young male patients with IBD only in cases in which a clear benefit is expected, such as in early stage disease in untreated patients or possibly in very severe cases.

Section snippets

Methods

A systematic review of the literature was performed. Databases of literature examined included MEDLINE, EMBASE, the Cochrane Database, Journals@OVID, CAB, and OVID Healthstar. Search terms included a search for the keywords “hepatosplenic” and “lymphoma” with the Boolean operator “AND.” To be included, articles and abstracts required presentation of cases of concurrent IBD and HSTCL. Additional articles were identified in reference lists of selected articles. Non-English articles and abstracts

Results

Thirty-six patients were reported to have developed HSTCL after treatment for IBD since 1996, of whom 20 also were exposed to anti-TNF therapies.1, 2, 3, 4, 9, 11, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 The range of known patients' ages was 12 to 58 years, with a median age of 22.5 years (Supplementary Table 1).1, 2, 3, 4, 10, 11, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27 Of the 31 patients whose gender was known, 2 (6.5%) were women. With respect to subtype of IBD,

Discussion

Overall, there have been approximately 100 to 200 cases of HSTCL reported in the literature in the past 18 years1, 3, 4, 5; 36 of these cases have occurred in IBD patients exposed to thiopurines. Although reporting bias may play a role, it nonetheless appears likely that patients with IBD are overrepresented in the cases of HSTCL.

From the National Cancer Institute's Surveillance, Epidemiology and End Results database, there were about 157,824 cases of non-Hodgkin's lymphoma from 2001 to 2007;

Acknowledgments

The authors appreciate and acknowledge the assistance of Gerald Falchook, Laurent Beaugerie, and Elizabeth Fowler in providing additional information about their published work.

References (48)

  • D. Kotlyar et al.

    S1133 hepatosplenic T-cell lymphoma (HSTCL) and IBD: a rare complication after long-term thiopurine exposure: case report and systematic review of the literature

    Gastroenterology

    (2009)
  • A.C. Mackey et al.

    Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease: update

    J Pediatr Gastroenterol Nutr

    (2009)
  • A.C. Mackey et al.

    Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease

    J Pediatr Gastroenterol Nutr

    (2007)
  • M. Shale et al.

    Hepatosplenic T cell lymphoma in inflammatory bowel disease

    Gut

    (2008)
  • Data on file, Centocor, Inc, Horsham,...
  • L. Beaugerie et al.

    Excess risk of lymphoproliferative disorders (LPD) in inflammatory bowel diseases (IBD): interim results of the CESAME cohort

    Gastroenterology

    (2008)
  • A. Kandiel et al.

    Increased risk of lymphoma among inflammatory bowel disease patients treated with azathioprine and 6-mercaptopurine

    Gut

    (2005)
  • D.S. Kotlyar et al.

    Hepatosplenic T-cell lymphoma in inflammatory bowel disease: a possible thiopurine-induced chromosomal abnormality

    Am J Gastroenterol

    (2010)
  • J.R. Rosh et al.

    Hepatosplenic T-cell lymphoma in adolescents and young adults with Crohn's disease: a cautionary tale?

    Inflamm Bowel Dis

    (2007)
  • M. Drini et al.

    Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease

    Med J Aust

    (2008)
  • M.R. Humphreys et al.

    Long-term survival in two patients with hepatosplenic T cell lymphoma treated with interferon-alpha

    Leuk Lymphoma

    (2008)
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    Conflicts of interest These authors disclose the following: Gary Lichtenstein has received compensation for research/grant support, support for lectures, and for support for being a member of the scientific advisory committee from the following companies: Centocor, Abbott, UCB, Bristol Meyers-Squibb, Elan, and Prometheus; Robert H. Diamond and Sami Sampat are employees of Centocor Ortho Biotech. The remaining authors disclose no conflicts.

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