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Meta-Analysis
. 2013 Oct 29;2013(10):CD008983.
doi: 10.1002/14651858.CD008983.pub2.

Influenza vaccines in immunosuppressed adults with cancer

Noa Eliakim-Raz  1 , Inbal Vinograd, Anca Zalmanovici Trestioreanu, Leonard Leibovici, Mical Paul
Affiliations
Meta-Analysis

Influenza vaccines in immunosuppressed adults with cancer

Noa Eliakim-Raz et al. Cochrane Database Syst Rev. .

Update in

  • Influenza vaccines in immunosuppressed adults with cancer.
    Bitterman R, Eliakim-Raz N, Vinograd I, Zalmanovici Trestioreanu A, Leibovici L, Paul M. Bitterman R, et al. Cochrane Database Syst Rev. 2018 Feb 1;2(2):CD008983. doi: 10.1002/14651858.CD008983.pub3. Cochrane Database Syst Rev. 2018. PMID: 29388675 Free PMC article.

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.

Objectives: 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.

Search 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 Finally, we searched for ongoing or unpublished trials in clinical trial registry databases using the website.

Selection criteria: 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.

Data collection and analysis: 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.

Main 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).

Authors' 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.

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Conflict of interest statement

None

Figures

Figure 1
Figure 1
Study flow diagram.
Analysis 1.1
Analysis 1.1
Comparison 1 Influenza vaccine versus none, Outcome 1 All‐cause mortality.
Analysis 1.2
Analysis 1.2
Comparison 1 Influenza vaccine versus none, Outcome 2 Influenza‐like illness.
Analysis 1.3
Analysis 1.3
Comparison 1 Influenza vaccine versus none, Outcome 3 Confirmed influenza.
Analysis 1.4
Analysis 1.4
Comparison 1 Influenza vaccine versus none, Outcome 4 Pneumonia.
Analysis 1.5
Analysis 1.5
Comparison 1 Influenza vaccine versus none, Outcome 5 Any hospitalization.
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

    1. Earle C C. Influenza vaccination in elderly patients with advanced colorectal cancer. Journal of Clinical Oncology 2003;21(6):1161‐6. - PubMed
    1. Machado CM, Cardoso MRA, Rocha IF, Boas LSV, Dulley FL, Pannuti CS. The benefit of influenza vaccination after bone marrow transplantation. Bone Marrow Transplantation 2005;36:897‐900. - PubMed
    1. Musto P, Carotenuto M. Vaccination against influenza in multiple myeloma. British Journal of Haematology 1997;97(2):504‐10. - PubMed
    1. Vinograd I, Eliakim‐Raz N, Farbman L, Baslo R, Taha A, Sakhnini A, et al. Clinical effectiveness of seasonal influenza vaccine among adult cancer patients. Cancer 2013;16 SEP:Epub ahead of print. [10.1002/cncr.28351] - PubMed

References to studies excluded from this review

    1. Adell C, Bayas JM, Vilella A, Perales M, Vidal J, Bertran MJ, et al. Post‐transplantation vaccination of bone‐marrow transplant recipients [Vacunacion de pacientes receptores de trasplante de progenitores hematopoyeticos]. Medicina Clinica Journal 2002;119(11):405‐9. - PubMed
    1. Anderson H, Petrie K, Berrisford C, Charlett A, Thatcher N, Zambon M. Seroconversion after influenza vaccination in patients with lung cancer. British Journal of Cancer 1999;80:219‐20. - PMC - PubMed
    1. Avetisyan G, Aschan J, Hassan M, Ljungman P. Evaluation of immune responses to seasonal influenza vaccination in healthy volunteers and in patients after stem cell transplantation. Transplantation 2008;86(2):257‐63. - PubMed
    1. Bedognetti D, Zoppoli G, Massucco C, Zupo S, Sertoli MR. Impaired humoral response to influenza vaccine and prolonged B memory cell depletion as a consequence of rituximab‐based immunochemotherapy in non‐hodgkin lymphoma patients. Journal of Immunotherapy 2009;32(9):992–3.
    1. Bedognetti D, Zoppoli G, Zanardi E, Massucco C, Sertoli MR. Prolonged lack of humoral response to influenza vaccine associated with a persistent depletion of B memory cells in non‐hodgkin’s lymphoma patients treated with rituximab‐containing immunochemotherapy. Clinical Immunology 2010;135:84. - PubMed

Additional references

    1. Alistair R, Gavin M, Christopher S, Peter H. Influenza vaccination and chemotherapy: a shot in the dark?. Supportive Care in Cancer 2002;10:462‐65. - PubMed
    1. Anema A, Mills E, Montaner J, Brownstein JS, Cooper C. Efficacy of influenza vaccination in HIV‐positive patients: a systematic review and meta‐analysis. HIV Medicine 2008;9(1):57‐61. - PubMed
    1. Angelo SJ, Marshall PS, Chrissoheris MP, Chaves AM. Clinical characteristics associated with poor outcome in patients acutely infected with Influenza A. Connecticut Medicine 2004;68:199‐205. - PubMed
    1. Arrowood JR, Hayney MS. Immunization recommendations for adults with cancer. Annals of Pharmacotherapy 2002;36:1219‐29. - PubMed
    1. Centers for Disease Control and Prevention. Cancer prevention and control. Available from: http://www.cdc.gov/cancer/flu/ (accessed 12th December 2010).

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