Tumor necrosis factor inhibitors and acute leukemia in two cases.

e18010 Background: Inhibitors of tumor necrosis factor alpha (anti-TNF agents) are commonly used in Crohn’s disease and rheumatoid arthritis. Relationship between TNF inhibitors and development of malignancy, e.g., lymphoma and solid tumors, is defined recently. However, a few authors reported leukemia. Crohn’s disease and also azothioprine may also be associated with leukemia. Here, we are presenting two acute myeloid leukemia (AML) cases using azothioprine and anti-TNF inhibitors for Crohn’s disease. Methods: Observational case report. Results: Case 1: A 56-year-old male patient with active Crohn’s disease for 4 years was refractory to first line mesalazine, corticosteroid and azothioprine treatment. So, anti-TNF monoclonal antibody (moAb) (Adalimumab) had been given. After second dose of adalimumab treatment AML (AML-M2 as FAB) developed. Case 2: A 38-year-old male had been diagnosed with ankylosing spondylitis for 7 years and Crohn’s disease for 2 years. He had been treated with salazopyrin and indomethacin. Anti-TNF etanercept (50 mg/wk) was started 30 months ago due to severe active pulmonary disease. After 1 year, he developed active Crohn’s disease. So, the treatment changed to infliximab. Also, mesalazine and azothioprine were added to treatment. On the 18th month of the infliximab t(15;17) positive acute promyelocytic leukemia were developed in the patient. Conclusions: Blocking TNF with anti TNF agents may cause blocking apoptosis and inhibit natural killer activity. So, antitumoral activity of natural killer cells is blocked by these agents. TNF alpha gene mutation has been associated with CLL, lymphoma, myelodysplastic syndrome and secondary AML. Azothioprine may also increase leukemia, lymphoma and solid tumors risk at patient on anti TNF treatment. Following the diagnosis of Crohn’s disease without immunomodulator treatment a case had developed acute leukemia in the literature. In our patients, anti-TNF, azothioprine and inflammatory bowel disease may be cause acute leukemia cumulatively. Physicians should be careful and regularly check the patients using anti-TNF agents in considering of malignancy development. In conclusion, the pathogenesis of leukemia development after TNF blockage should be clarified.

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New Onset, Aggravation and Recurrence of Crohn's Disease upon Treatment with Three Different Tumor Necrosis Factor Inhibitors

Case Reports in Gastroenterology ◽

10.1159/000381637 ◽

2015 ◽

Vol 9 (1) ◽

pp. 106-112 ◽

Cited By ~ 5

Author(s):

Jonas Zeitz ◽

Susann Enderlin ◽

Luc Biedermann ◽

Matthias Turina ◽

Sebastian Leibl ◽

...

Keyword(s):

Crohn’S Disease ◽

Tumor Necrosis Factor ◽

Crohn's Disease ◽

Tumor Necrosis ◽

Tnf Inhibitors ◽

Etanercept Treatment ◽

Abdominal Symptoms ◽

Long Term Treatment ◽

Tnf Inhibition ◽

Necrosis Factor

Tumor necrosis factor (TNF) is a major cytokine in the pathogenesis of inflammatory bowel disease (IBD), and TNF inhibition is a cornerstone of contemporary IBD therapy. However, paradoxical induction of IBD has recently been reported upon treatment of rheumatologic disorders with TNF inhibitors. In previous cases, induction of IBD was associated with one single drug and IBD was successfully managed by switching TNF inhibitors. We report the case of a patient with juvenile rheumatoid arthritis under long-term treatment with etanercept. After switching TNF inhibition to adalimumab, symptoms of Crohn's disease (CD) occurred and the diagnosis of CD was established by endoscopy. Further treatment with adalimumab and subsequently infliximab aggravated the abdominal symptoms, necessitating ileocecal resection, after which symptoms resolved for several months. Etanercept treatment due to recurrent rheumatologic symptoms was followed by recurrent CD symptoms and findings, which resolved upon discontinuation of etanercept. This case suggests that induction, aggravation and recurrence of IBD can be rare class effects of TNF inhibition.

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