Hepatosplenic T Cell Lymphoma Associated With Infliximab Use in Young Patients Treated for Inflammatory Bowel Disease

Abstract

Hepatosplenic T cell lymphoma (HSTCL) are rare cancers ( approximately 100 published cases worldwide) and comprise 5% of peripheral T cell lymphomas. As of October 5, 2006, the FDA's Adverse Event Reporting System has received 8 cases of HSTCL in young patients using infliximab, a tumor necrosis factor-alpha blocking agent, to treat inflammatory bowel disease (6 of the 8 cases had a fatal outcome). All 8 patients were receiving concomitant immunosuppressant therapy (eg, azathioprine, prednisone). It has not been established that infliximab had an exclusive or primary role in the pathogenesis of these HSTCL cases; however, it appears that patients using this product may be at greater risk for developing this rare lymphoma.

Two Cases of Hepatosplenic T-Cell Lymphoma in Adolescents Treated for Autoimmune Hepatitis

“…8 In the group of IBD patients, HSTCL has been described since 2007. 9 An international warning derived from the observation that IBD patients treated with anti-TNFs developed fatal HSTCL (especially young males). But as a result of recently published data regarding risk factors for HSTCL in patients with IBD that showed that most patients received a combination of thiopurines and anti-TNFs, the discussion emerged that not only are the anti-TNFs risk factors, but also thiopurines themselves or the combination of both.…”

Management of Crohn's Disease in Adults

“…Lymphomas that have occurred during thiopurine therapy have increasingly been recognized to be related to Epstein -Barr infections (216,217,221) . A rare form of natural killer cell, hepatosplenic lymphoma has recently been described associated with azathioprine therapy for CD either alone (222) or in combination with in iximab (223,224) . Weekly methotrexate at a dose of 15 mg, intramuscularly, has also been demonstrated to maintain methotrexate-induced remissions (225) , but optimal dosing has not been established (15,17,226,227) .…”

Autoimmune Disorders and Lymphomas

“…The only exception is constituted by 8 cases of hepatosplenic  T-cell lymphoma diagnosed among young patients treated with infliximab or adalimumab for inflammatory bowel disease. All patients were receiving concomitant immunosuppressive therapy with azathioprine or prednisone and it was not possible to ascertain if anti-TNF medication had an exclusive role in the pathogenesis of these lymphomas (Mackey et al, 2007). Conversely, although it has not been definitively demonstrated, postponing therapy could contribute to lymphoma development; this could be due to a chronic worsening of the inflammatory microenvironment promoted by uncontrolled disease.…”