Etoposide-based therapy may reduce mortality from bird flu

Based on its similarity to the immune disorder hemophagocytic lymphohistiocytosis (HLH), researchers theorize that severe cases of human H5N1 infection may respond to HLH therapy dexamethasone plus etoposide along with antiviral drugs and relevant supportive therapy.

Dr. Jan-Inge Henter, from Karolinska Institutet in Stockholm, and colleagues in Hong Kong explain that HLH and avian influenza are characterized by massive hypercytokinemia, cytopenia, and acute encephalitis. The cause of death in both conditions is often sepsis-related with multiorgan failure.Moreover, they note in their report in The Lancet published online on March 2, studies have shown that the high mortality rate of Epstein-Barr virus-associated HLH is significantly reduced by HLH treatment.Dr. Henter’s team notes that etoposide induces apoptosis, and dexamethasone has pro-apoptotic effects on mononuclear cells, which would result in downregulation of the inflammatory response.Based on its success in treating secondary HLH, the authors suggest that “it could be ethically justified to initially use (up to 8 weeks) this treatment for patients with H5N1 infection and secondary HLH,” along with antiviral therapy and monitoring of viral load.Secondary HLH is diagnosed based on five of eight criteria: fever, splenomegaly, bicytopenia, hypertriglyceridemia or hypofibrinogenemia (or both), hemophagocytosis, ferritin > 500ug/L, low natural killer cell activity, and soluble interleukin-2 receptor > 2400 U/mL.Their advice is to initially use weekly etoposide doses of 100 mg/ml2 in patients ages 15 or older, and 50 mg/ml2 in middle-age and elderly patients.Dr. Henter and his colleagues urge that physicians report cases in which HLH therapy is used to the HLH Study Centre at the Karolinska Institute, and that the “WHO consider a platform for the undertaking of clinical trials based on a modified HLH protocol (including corticosteroids and etoposide) in addition to supportive and antiviral therapy.”(Source: Lancet 2006: Reuters Health: Oncolink: March 2006.)