Hepatosplenic T‐cell lymphoma, immunosuppressive agents and biologicals: what are the risks?

Abstract

We present three cases of the rare hepatosplenic T-cell lymphoma (HSTCL); two patients suffering from Crohn disease who developed HSTCL on azathioprine without exposure to biologicals, and a third patient who had psoriasis treated using etanercept, cyclosporine and methotrexate. The evidence for an association between HSTCL and immunosuppressive drugs and biologicals is reviewed. We argue for improved pharmacovigilance processes to help determine the benefit to risk ratios for the use of these and other new agents.

Immune thrombocytopenia: Effectiveness of frontline steroids and comparison of azathioprine, splenectomy, and rituximab as second‐line treatment

“…Azathioprine was reported to cause alopecia, hepatotoxicity, myelosuppression, and gastrointestinal adverse effects . An increased risk of malignancy (mainly lymphoma) has been noted . According to our experience,16% of patients developed reversible hepatic dysfunction and leukopenia, respectively.…”

“…32 An increased risk of malignancy (mainly lymphoma) has been noted. 33,34 According to our experience,16% of patients developed reversible that the risk of both azathioprine and splenectomy may have been underestimated in our study, as the cases were enrolled in a crosssection survey in the outpatient cohort and the data were collected in a retrospective manner. Nevertheless, both splenectomy and azathioprine are associated with relatively good response rates and minimal toxicities.…”

Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

“…Certainly, one interesting hypothesis to explain a potential association is that azathioprine impairs the immune system's ability to correct dysplasia that can occur in the inflammatory environment created by CD. The known hepatotoxicity of azathioprine as well as its association with malignancies such as lymphoma [ 9 ] lends support to this theory. In our case, the regression of the HCC between the initial biopsy and surgical resection potentially supports this hypothesis as azathioprine was stopped prior to surgery, thereby promoting immune function which may have contributed to the regression of the cancer.…”

Hepatosplenic T cell lymphoma presenting as multiorgan failure

“…We present the first case of HSTCL in an immunocompetent female in Australia who presented with hepatosplenomegaly, no lymphadenopathy and no peripheral lymphocytosis with thrombocytopenia and moderate anaemia. To the best of our knowledge, there are four cases of HSTCL published in Australia and all of these patients had HSTCL in the setting of exposure to immunomodulators or TNF-alpha inhibitors 1 2…”