title: Influenza vaccination in children being treated with chemotherapy for cancer.
abstract: BACKGROUND
  Influenza infection is a potential cause of severe morbidity in children with cancer; therefore vaccination against influenza is recommended. However, data are conflicting regarding the immune response to influenza vaccination in children with cancer, and the value of vaccination remains unclear.
  
  
  OBJECTIVE
  1. To assess the efficacy of influenza vaccination in stimulating an immunological response in children with cancer during chemotherapy, compared with control groups.2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or in stimulating immunological response in children with cancer treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.3. To identify the adverse effects associated with influenza vaccines in children with cancer treated with chemotherapy, compared with other control groups.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2012) and EMBASE (1980 to 2012) up to August 2012. We also searched reference lists of relevant articles and conference proceedings of the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), the Infectious Diseases Society of America (IDSA), the Multinational Association of Supportive Care in Cancer (MASCC) and the International Society of Paediatric Oncology (SIOP).
  
  
  METHODS
  We considered randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which the serological response to influenza vaccination of children with cancer was compared with that of control groups. We also considered RCTs and CCTs that compared the effects of influenza vaccination on clinical response and/or immunological response in children with cancer being treated with chemotherapy, compared with placebo, no intervention or different dosage schedules.
  
  
  METHODS
  Two independent review authors assessed the methodological quality of included studies and extracted the data.
  
  
  RESULTS
  We included 1 RCT and 9 CCTs (total number of participants = 770). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reactions to vaccination. In five studies, immune responses to influenza vaccine were compared in 272 children receiving chemotherapy and 166 children not receiving chemotherapy. In four studies, responses to influenza vaccine were assessed in 236 children receiving chemotherapy compared with responses in 142 healthy children. Measures used to assess immune responses included a four-fold rise in antibody titre after vaccination, development of a haemagglutination inhibition (HI) titre > 32 and pre- and post-vaccination geometric mean titres (GMTs). Immune responses in children receiving chemotherapy were consistently weaker (four-fold rise of 38% to 65%) than those in children who had completed chemotherapy (50% to 86%) and in healthy children (53% to 89%). In terms of adverse effects, 391 paediatric oncology patients received influenza vaccine, and the adverse effects described included mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported.
  
  
  CONCLUSIONS
  Paediatric oncology patients receiving chemotherapy are able to generate an immune response to the influenza vaccine, but it remains unclear whether this immune response protects them from influenza infection or its complications. We are awaiting results from well-designed RCTs addressing the clinical benefit of influenza vaccination in these patients.
authors.affiliation: Faculty of Medical Sciences, Erasmus MC - Sophia Children's Hospital, PO Box 2060, Rotterdam, Netherlands, 3000 CB.
authors.forename: Ginette M
authors.initials: GM
authors.lastname: Goossen
authors.forename: Leontien C M
authors.initials: LC
authors.lastname: Kremer
authors.forename: Marianne D
authors.initials: MD
authors.lastname: van de Wetering
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002648:Child; D018849:Controlled Clinical Trials as Topic; D006801:Humans; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D007252:Influenza Vaccines
references.citation: J Infect Dis. 1977 Dec;136 Suppl:S656-60
references.pmid: 606789
references.citation: J Pediatr. 1978 Jan;92(1):30-5
references.pmid: 619076
references.citation: Am J Med. 1997 Mar 17;102(3A):48-52; discussion 53-4
references.pmid: 10868143
references.citation: J Infect Dis. 1979 Sep;140(3):402-6
references.pmid: 291662
references.citation: Leuk Lymphoma. 1997 Jun;26(1-2):163-9
references.pmid: 9250801
references.citation: Pediatr Blood Cancer. 2004 Jan;42(1):36-40
references.pmid: 14752792
references.citation: Cochrane Database Syst Rev. 2009 Apr 15;(2):CD006484
references.pmid: 19370636
references.citation: Schweiz Med Wochenschr Suppl. 1983;14:30-4
references.pmid: 6581531
references.citation: J Pediatr. 1989 Jul;115(1):33-9
references.pmid: 2738793
references.citation: Am J Manag Care. 2000 Mar;6(5 Suppl):S247-54
references.pmid: 10977471
references.citation: J Infect Dis. 1982 Jan;145(1):126
references.pmid: 7054313
references.citation: J Infect Dis. 1977 Dec;136 Suppl:S626-31
references.pmid: 606784
references.citation: J Pediatr. 1978 Oct;93(4):632-4
references.pmid: 702243
references.citation: Pediatr Pol. 1996 Apr;71(4):301-6
references.pmid: 8975216
references.citation: Rev Infect Dis. 1985 Sep-Oct;7(5):613-8
references.pmid: 3903940
references.citation: Pediatr Blood Cancer. 2010 May;54(5):716-20
references.pmid: 20205258
references.citation: Expert Opin Ther Targets. 2005 Feb;9(1):1-22
references.pmid: 15757479
references.citation: Cancer Res. 1971 Apr;31(4):420-6
references.pmid: 4994993
references.citation: Cancer. 1980 Feb 15;45(4):750-6
references.pmid: 7357492
references.citation: J Pediatr Hematol Oncol. 2010 Jul;32(5):e177-81
references.pmid: 20485201
references.citation: Ann Oncol. 2006 Jul;17(7):1051-9
references.pmid: 16410361
references.citation: Med Clin (Barc). 2002 Oct 5;119(11):405-9
references.pmid: 12381273
references.citation: Arch Dis Child. 2001 Jun;84(6):496-500
references.pmid: 11369567
references.citation: Zh Mikrobiol Epidemiol Immunobiol. 1999 Jul-Aug;(4):30-4
references.pmid: 10852046
references.citation: J Infect Dis. 1977 Dec;136 Suppl:S672-6
references.pmid: 606790
references.citation: J Formos Med Assoc. 2002 Oct;101(10):700-4
references.pmid: 12517044
references.citation: Pediatr Blood Cancer. 2007 Dec;49(7):914-7
references.pmid: 17262793
references.citation: Biken J. 1982 Jun;25(2):89-95
references.pmid: 6753829
references.citation: Pediatr Infect Dis J. 1995 Aug;14(8):690-4
references.pmid: 8532427
references.citation: J Pain Symptom Manage. 2000 May;19(5):363-77
references.pmid: 10869877
references.citation: Vaccine. 2003 Jan 30;21(7-8):601-4
references.pmid: 12531325
references.citation: Curr Opin Crit Care. 2001 Oct;7(5):362-6
references.pmid: 11805534
references.citation: Pediatrics. 1982 Feb;69(2):226-9
references.pmid: 7058098
references.citation: Cancer. 2003 May 15;97(10):2576-87
references.pmid: 12733157
references.citation: Biol Blood Marrow Transplant. 2001;7 Suppl:19S-22S
references.pmid: 11777100
references.citation: Cancer. 1978 Nov;42(5):2244-7
references.pmid: 719604
references.citation: Helv Med Acta. 1974 May;37(5-6):395
references.pmid: 4410562
references.citation: Can Med Assoc J. 1978 Oct 7;119(7):733,-5, 738
references.pmid: 709474
references.citation: Pediatr Infect Dis J. 1998 Feb;17(2):125-9
references.pmid: 9493808
references.citation: Leuk Lymphoma. 1993 Feb;9(3):177-92
references.pmid: 8471977
references.citation: MMWR Recomm Rep. 2010 Aug 6;59(RR-8):1-62
references.pmid: 20689501
references.citation: Cancer. 1979 Jan;43(1):25-30
references.pmid: 761165
references.citation: Aust Paediatr J. 1979 Sep;15(3):177-80
references.pmid: 293160
references.citation: J Clin Pathol. 1991 Apr;44(4):297-9
references.pmid: 2030147
references.citation: Pediatr Blood Cancer. 2005 Nov;45(6):831-7
references.pmid: 16007602
references.citation: Clin Infect Dis. 2000 Feb;30(2):342-8
references.pmid: 10671339
references.citation: Eur J Cancer. 2005 Oct;41(15):2280-7
references.pmid: 16143516
references.citation: Pediatrics. 2006 Apr;117(4):e610-8
references.pmid: 16585278
references.citation: Acta Haematol. 1994;91(3):115-8
references.pmid: 8091931
references.citation: Cancer. 1977 Jan;39(1):350-3
references.pmid: 576210
references.citation: Am J Med. 1995 Apr;98(4):389-98
references.pmid: 7709953
references.citation: Hum Vaccin. 2009 Jun;5(6):430-2
references.pmid: 19221519
references.citation: Support Care Cancer. 2002 Sep;10(6):462-5
references.pmid: 12353124
references.citation: Bone Marrow Transplant. 1993 Jan;11(1):1-5
references.pmid: 8431706