title: Influenza vaccines in immunosuppressed adults with cancer.
abstract: BACKGROUND
  Immunosuppressed cancer patients are at increased risk of serious influenza-related complications. Guidelines, therefore, recommend influenza vaccination for these patients. However, data on vaccine effectiveness in this population is lacking, and the value of vaccination in this population remains unclear.
  
  
  OBJECTIVE
  To assess the effectiveness of influenza vaccine in immunosuppressed adults with malignancies. The primary review outcome is all-cause mortality, preferably at the end of the influenza season. Influenza-like illness (ILI, a clinical definition), confirmed influenza, pneumonia, any hospitalization and influenza-related mortality were defined as secondary outcomes.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS databases up to August 2013. We searched the following conference proceedings: ICAAC, ECCMID, IDSA (infectious disease conferences), ASH, ASBMT, EBMT (hematological), and ASCO (oncological) between the years 2006 to 2010. In addition, we scanned the references of all identified studies and pertinent reviews. We searched the websites of the manufacturers of influenza vaccine. Finally, we searched for ongoing or unpublished trials in clinical trial registry databases using the website.
  
  
  METHODS
  Randomized controlled trials (RCTs), prospective and retrospective cohort studies and case-control studies were considered, comparing inactivated influenza vaccines versus placebo, no vaccination or a different vaccine, in adults (16 years and over) with cancer. We considered solid malignancies treated with chemotherapy, haematological cancer patients treated or not treated with chemotherapy, cancer patients post-autologous (up to six months after transplantation) or allogeneic (at any time) hematopoietic stem cell transplantation.
  
  
  METHODS
  Two review authors independently assessed the risk of bias and extracted data from included studies adhering to Cochrane methodology. Meta-analysis could not be performed because of different outcome and denominator definitions in the included studies.
  
  
  RESULTS
  We identified four studies: one RCT and three observational studies, including 2124 participants. One study reported results in person-years while the other three reported per person. The studies were performed between 1993 and 2012 and included adults with haematological diseases (two studies), patients following bone marrow transplantation (one study) and solid malignancies (three studies). Only two observational studies reported all-cause mortality; one showing an adjusted hazard ratio (HR) of 0.88 (95% CI 0.77 to 0.99) for death with vaccination and the other reporting an odds ratio (OR) of 0.43 (95% CI 0.26 to 0.71). The RCT reported a statistically significant reduction in ILI with vaccination, while no difference was observed in one observational study. Confirmed influenza rates were lower with vaccination in the three observational studies, the difference reaching statistical significance in one. Pneumonia was observed significantly less frequently with vaccination in one observational study, but no difference was detected in another or in the RCT. The RCT showed a reduction in hospitalizations following vaccination, while an observational study found no difference. No life-threatening or persistent adverse effects from vaccination were reported. The strength of evidence is limited by the low number of included studies and by their low methodological quality (high risk of bias).
  
  
  CONCLUSIONS
  Observational data suggests a lower mortality with influenza vaccination. Infection-related outcomes were lower or similar with influenza vaccination. The strength of evidence is limited by the small number of studies and by the fact that only one was a RCT. Influenza vaccination is safe and the evidence, although weak, is in favour of vaccinating adults with cancer receiving chemotherapy.
authors.affiliation: Department of Medicine E, Beilinson Hospital, Rabin Medical Center, 39 Jabotinski Street, Petah Tikva, Israel, 49100.
authors.forename: Noa
authors.initials: N
authors.lastname: Eliakim-Raz
authors.forename: Inbal
authors.initials: I
authors.lastname: Vinograd
authors.forename: Anca
authors.initials: A
authors.lastname: Zalmanovici Trestioreanu
authors.forename: Leonard
authors.initials: L
authors.lastname: Leibovici
authors.forename: Mical
authors.initials: M
authors.lastname: Paul
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D016022:Case-Control Studies; D002423:Cause of Death; D015331:Cohort Studies; D019337:Hematologic Neoplasms / Q000276:immunology / Q000401:mortality; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage* / Q000276:immunology; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D009369:Neoplasms / Q000276:immunology* / Q000401:mortality; D064887:Observational Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D007252:Influenza Vaccines