Evaluation of efficacy and safety of an enhanced influenza vaccination schedule in immunocompromised children undergoing treatment for cancer.

Study interventions Participants in the 6 months to <9 years group will be asked to present for 4 visits in total, spaced by 4-6 weeks. The first 3 visits will comprise of the influenza vaccine injection and obtaining study blood samples. The 4th and last visit is an exit visit that will comprise of obtaining study samples only. Participants in the 9 years to 18 years group will be asked to present for 3 visits in total, spaced by 4-6 weeks. The first 2 visits will comprise of the influenza vaccine injection and obtaining study blood samples. The 3rd and last visit is an exit visit that will comprise of obtaining study samples only. Each visit (with the exception of the exit visit) will comprise of two main components: 1. A blood sample will be taken to perform the following tests: a. A full blood count (FBC) including the differential will be requested prior each vaccination. Vaccination will only proceed if absolute neutrophil count (ANC) is geater than or equal to 0.5 x 109/L, as per the Australian Immunisation Handbook 10th Edition recommendations. b. Lymphocyte subsets (Visit 1 only). This is to measure the number of B-cells, CD4 and CD8 positive T-cells, NK cells and memory T and B-cells. c. IgG, IgA and IgM levels (Visit 1 only). d. Cellular response to the influenza vaccine. e. HI antibody titer measurement. 2. Influenza vaccine injection will be given (with the exception of the exit visit) to the participant after a baseline medical check. Participants found to be physically unfit, after an examination performed by the oncology team doctor, will have their vaccination postponed. The influenza vaccine injection will be administered by an oncology nurse either in the outpatient or inpatient setting. A minimum 30 minute observation period will be provided to monitor for development of an acute adverse event following vaccination (AEFI). Study visits will be spaced by a minimum of 4 weeks and maximum of 6 weeks as per the Australian Immunisation Handbook 10th Edition recommendations regarding timing of influenza vaccination and to allow for flexibility in arranging suitable appointments for study participants. The influenza vaccine used in the study will be: FluQuadri For all study participants irrespective of the age Administration route: intramuscular injection Sponsor: Sanofi-Aventis Australia Quadrivalent inactivated influenza vaccine Each 0.5 mL pre-filled syringe contains: 15 µg hemagglutinin for each of the 4 recommended influenza virus strains =100 µg formaldehyde =250 µg octoxinol 9 =1 µg ovalbumin Any AEFIs will be documented at each visit. Each participant’s parent/guardian will also be contacted by telephone one week after the influenza vaccination to document any delayed AEFIs related to the influenza vaccine. Participants who develop an influenza-like illness (ILI) during the study period will be asked to contact the study team, except in the case of a fever defined as an isolated temperature of more or equal to 38.5°C, or two temperatures of more or equal to 38.0°C in 12 hours; when they would present to the Emergency Department as per the standard Oncology Department guidelines. ILI is defined by the following criteria, occurring greater than 72 hours after influenza vaccine administration: • Elevated temperature (>37.5°C) or a clear history of fever (chills, rigors) AND • Presence of at least one respiratory symptom such as: o Cough o Sore throat o Rhinorrhoea Participants reporting symptoms of an ILI will be asked to present for a review. A nasopharyngeal test will be collected for virological testing at the time of the visit should their symptoms be objectively confirmed by the study team. Patients who present to the Emergency Department with a fever will be admitted to the Oncology ward as per the standard pathway and a nasopharyngeal test will be collected for virological testing.