Hepatosplenic T-cell lymphoma and inflammatory bowel disease

University of California, Davis Medical Center (UCDMC), Internal Medicine, 4150 V Street, Suite 3100, Sacramento, CA 95817, United States.
Journal of Crohn s and Colitis (Impact Factor: 6.23). 11/2010; 4(5):511-22. DOI: 10.1016/j.crohns.2010.05.006
Source: PubMed


This article reviews the current literature and knowledge about hepatosplenic T-cell lymphoma (HSTCL), providing an overview of the clinical features, a description of its pathology and immunophenotypic traits in relation to other lymphomas. In addition, we explore the history of reported cases of hepatosplenic T-cell lymphoma in relation to the possible existence of a causal relationship between infliximab use and HSTCL. The treatments for HSTCL will be briefly addressed.
A comprehensive literature search using multiple databases was performed. Keyword search phrases including "lymphoma," "hepatosplenic T-cell lymphoma," "Inflammatory bowel disease," "6-mercaptopurine," and "infliximab" were used in various combinations. In addition references from published papers were reviewed as well.
There are over 200 reported cases of HSTCL. Only 22 cases of hepatosplenic T-cell lymphoma are associated with IBD treatment. Clinicians usually reserve immunomodulators and biologics for moderate to severe IBD cases. The ultimate goal of therapy is to control inflammation and therefore allow mucosal healing. IBD patients demonstrating mucosal healing are less likely to undergo surgery and experience complications related to their disease. We manipulate the immune system with corticosteroids, immunomodulators, and biologics, therefore causing bone marrow suppression. With bone marrow suppression, malignant degeneration may begin through selective uncontrolled cell proliferation, initiating HSTCL development in the genetically susceptible.
Hepatosplenic T-cell lymphoma is a rare disease, often with a poor outcome. With the increasing number of reported cases of HSTCL linked to the use of infliximab, adalimumab, and AZA/6-MP, there appears to be an undeniable association of HSTCL development with the use of these agents. This risk is unquantifiable. When considering the rarity of cases and the multiple complications with uncontrolled disease, however, the benefit of treatment far outweighs the risk.

Full-text preview

Available from:
  • Source
    • "The labels for natalizumab and ustekinumab do not mention lymphoma. The most common demographic risk factors were male sex and younger age, similar to previous studies [22,26,27]. No comparative study from the main systematic review included a case of HSTCL, and only one study specifically mentioned that no HSTCL cases were observed. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To identify demographic and clinical characteristics associated with cases of hepatosplenic T-cell lymphoma (HSTCL) in patients with Crohn's disease, and to assess strength of evidence for a causal relationship between medications and HSTCL in Crohn's disease. We identified cases of HSTCL in Crohn's disease in studies included in a comparative effectiveness review of Crohn's disease medications, through a separate search of PubMed and Embase for published case reports, and from the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS). We used three causality assessment tools to evaluate the relationship between medication exposure and HSTCL. We found 37 unique cases of HSTCL in patients with Crohn's disease. Six cases were unique to the published literature and nine were unique to AERS. Cases were typically young (<40 years of age) and male (86%). The most commonly reported medications were anti-metabolites (97%) and anti-tumor necrosis factor alpha (anti-TNFa) medications (76%). Dose and duration of therapy were not consistently reported. Use of aminosalicylates and corticosteroids were rarely reported, despite the high prevalence of these medications in routine treatment. Using the causality assessment tools, it could only be determined that anti-metabolite and anti-TNFa therapies were possible causes of HSTCL in Crohn's disease based on the data contained in the case reports. Systematic reviews that incorporate case reports of rare lethal events should search both published literature and AERS, but consideration should be given to the limitations of case reports. In this study, establishing a causative effect other than 'possible' between anti-metabolite or anti-TNFa therapies and HSTCL was not feasible because case reports lacked data required by the causality assessments, and because of the limited applicability of causality assessment tools for rare irreversible events. We recommend minimum reporting requirements for case reports to improve causality assessment and routine reporting of rare life-threatening events, including their absence, in clinical trials to help clinicians determine whether rare adverse events are causally related to a medication.
    Full-text · Article · Jul 2013 · Systematic Reviews
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The relation between Crohn’s colitis (CC) and colorectal cancer is still controversial. Several case reports and retrospective studies have shown that patients with Crohn’s disease (CD) have a 6- to 20-fold higher risk to develop CRC than does the normal population. The extent of disease (extensive colitis), presence of anal fistula, age > 40 years, strictures, and length of disease >10 years may be important determinants for increasing risk. Despite this evidence, other population-based studies have shown no increased risk of colon or rectal cancer. The aim of this study was to investigate retrospectively factors that may predict the development of cancer. Methods We searched the histopathologic database of the Digestive Surgery Unit at Careggi University Hospital for CC patients (January 1987 to September 2011) and identified 313 patients with CC who underwent surgery. Results There are 11 (3.5 %) of adenocarcinomas. Multivariate analysis showed disease duration (p = 0.001), age at CD diagnosis (p = 0.002), distal localization (p = 0.045), and penetrating disease (p = 0.041) to be risk factors. Multivariate analysis showed that 40 patients who had undergone previous immunosuppressive therapy had a significant risk of developing CRC (p = 0.026). Conclusions Crohn’s colitis patients who require surgery are at higher risk for developing CRC, particularly those whose disease duration is >10 years, have distal localization, age at diagnosis was <40 years, and have penetrating disease. Previous immunosuppressive therapy should be better investigated. We recommend surgery for any patient presenting with colonic strictures.
    No preview · Article · Apr 2013 · World Journal of Surgery
  • [Show abstract] [Hide abstract]
    ABSTRACT: Vibrating beam structures may be used as sensing elements in an angular rate measurement sensor. Achieving a square cross-sectional area with smooth vertical side walls and sharp edges is necessary for these beams. In this work, fabrication of beams with reasonably smooth vertical sidewalls and accurate dimensions, using anisotropic etching of silicon in TMAH, has been investigated. Beams with various thicknesses (500-100 microns) are fabricated. It is shown that by carefully aligning the mask at 45° from the 〈110〉 wafer flat, and by maintaining the concentration of TMAH at 25%, it is possible to achieve smooth vertical sidewalls with good uniformity along the length of the beam. Adequate control over the beam lateral dimension is achieved by etching in a 2-step procedure with the second step at a lower temperature (lower etch rate). Single-sided and double-sided masking techniques are investigated in order to fabricate the beams. An alternative design is presented to form the beams using a standard CMOS process
    No preview · Conference Paper · Jun 1996
Show more