Influenza burden and influenza vaccination in cancer

Abstract

Patients with cancer are at risk for post influenza complications due to their underlying disease as well as their (immunosuppressive) treatment; therefore influenza vaccination is recommended to prevent influenza infections. Adherence to vaccination recommendations is however low, most likely explained by the lack of evidence regarding efficacy/effectiveness and optimal timing of vaccination in this particular patient group. This thesis addresses the burden of influenza in adult patients with either haematological cancers or solid tumours and response to influenza virus vaccination as well as optimal timing of vaccination during the chemotherapy cycle in patients with malignancies treated with chemotherapy. To assess the burden of influenza, incidence of influenza and other respiratory virus infections in patients with acute myeloid leukemia (AML) was studied as well as excess mortality in cancer patients during the seasonal influenza period in the Netherlands. Forty-four percent of patients with AML presenting with fever and/or upper respiratory tract complaints tested positive for an influenza virus or other respiratory viruses, influenza viruses (A and B) accounted for most of the infections. Regarding excess mortality, a trend for higher number of cancer deaths was observed during influenza season in the Netherlands. Moreover, a trend was found for a positive association between influenza incidence and number of cancer deaths. The second part of this thesis addresses efficacy of vaccination; antibody responses and the broadness of the antibody response to influenza vaccination were studied in breast cancer and colorectal cancer patients. As a surrogate end-point of vaccine efficacy, the acquired antibody levels after vaccination are considered to be above threshold of protection (seroprotection) and increase in antibody titres (seroconversion) were presented. In breast cancer patients overall antibody responses were adequate. Statistically significant higher responses were observed in patients who received early vaccination (day 5 after chemotherapy) when compared to late vaccination (day 16). In colorectal cancer patients overall serologic responses were adequate with no statistically difference found between early and late vaccination. In addition to the determination of vaccine virus specific antibody titres in breast cancer patients, the broadness of the response was assessed by using a protein microarray consisting of 11 different influenza strains. A wide range in serum antibody response after vaccination was found, overall the response was broad because of the significant increase of antibodies against strains not represented in the vaccine. Higher age and previous influenza vaccination had a significant negative influence on the antibody response to the vaccine. Apart from vaccine efficacy, influenza vaccination coverage in the Netherlands was analyzed in breast cancer patients and colorectal cancer patients treated with chemotherapy. Fifty- nine percent of our study population were vaccinated against influenza. In case of non-adherence to the recommendations, lack of awareness, lack of optimal timing of the vaccination during the chemotherapy cycle, and concerns on efficacy of vaccination were given as reasons for not vaccinating. According to 48% of the general practitioners, the treating medical oncologist has the primary responsibility for vaccination. Better guidelines may increase the vaccination coverage of cancer patients.