Immunogenicity and clinical effectiveness of the trivalent inactivated influenza vaccine in immunocompromised children undergoing treatment for cancer

Abstract

Influenza is associated with significant morbidity and mortality in children receiving therapy for cancer, yet recommendation for, and uptake of the seasonal vaccine remains poor. One hundred children undergoing treatment for cancer were vaccinated with the trivalent inactivated influenza vaccine according to national guidelines in 2010 and 2011. Influenza‐specific hemagglutinin inhibition antibody titers were performed on blood samples taken prior to each vaccination and 4 weeks following the final vaccination. A nasopharyngeal aspirate for influenza was performed on all children who developed an influenza‐like illness. Following vaccination, seroprotection and seroconversion rates were 55 and 43% for H3N2, 61 and 43% for H1N1, and 41 and 33% for B strain, respectively. Overall, there was a significant geometric mean fold increase to H3N2 (GMFI 4.56, 95% CI 3.19–6.52, P < 0.01) and H1N1 (GMFI 4.44, 95% CI 3.19–6.19, P < 0.01) strains. Seroconversion was significantly more likely in children with solid compared with hematological malignancies and in children <10 years of age who received a two‐dose schedule compared to one. Influenza infection occurred in 2% of the vaccinated study population, compared with 6.8% in unvaccinated controls, providing an adjusted estimated vaccine effectiveness of 72% (95% CI −26–94%). There were no serious adverse events and a low reactogenicity rate of 3%. The trivalent inactivated influenza vaccine is safe, immunogenic, provides clinical protection and should be administered annually to immunosuppressed children receiving treatment for cancer. All children <10 years of age should receive a two‐dose schedule.

The Effectiveness of Trivalent Inactivated Influenza Vaccine in Children with Acute Leukemia

“…Kotecha et al followed 100 Australian pediatric oncology patients (<18 yrs of age) with a variety of oncologic diagnoses across 2 influenza seasons. 7 Although these authors did not describe outcomes of children with AL separately, their results appear consistent with those of the current study. Children with hematologic malignancies were significantly less likely to seroconvert or achieve seroprotection following vaccination than those with solid tumors, and most children with laboratory-confirmed influenza (11 of 13) had hematologic malignancies, including the only 2 children in the vaccinated study population who developed influenza.…”

“…3, 7, 28, 29 Younger patients in the current study, and those with higher lymphocyte counts were more likely to develop ILI, but not laboratory-confirmed influenza. Assuming that vaccine does not protect against influenza in this population, these associations may reflect intrinsic infection characteristics (e.g.…”

“…Children receiving therapy for solid tumors, for example, are more likely to seroconvert in response to influenza vaccination and may be more likely to benefit from vaccination. 7 Likewise, the majority of patients included in this study were treated at a single center on a single protocol, TOTAL XVI - other treatment regimens might have greater or lesser impact on host immunity and the effectiveness of TIV. We did not assess illness characteristics in this study, and cannot exclude the fact that TIV, although not protective against infection, modified the severity of illness in vaccinated children.…”

“…Treatment intensity was stratified as described by Kotecha. 7 Overall rates of disease (laboratory-confirmed influenza, the primary endpoint, and ILI, the secondary endpoint) were computed as the total number of cases divided by the total days at risk of infection. Demographic characteristics were compared across influenza season and vaccination status using the Wilcoxon rank sum or Kruskal-Wallis test for continuous variables and the Chi-square or Fisher’s exact test for categorical variables.…”

“…4, 6 The only study to address this question since the publication of these analyses suggested an overall benefit to pediatric oncology patients, but unclear effectiveness in children with hematologic malignancies. 7 We therefore reviewed the vaccination history and clinical course of patients receiving treatment for AL at a pediatric cancer center over three successive influenza seasons. The objectives of this study were to determine the effectiveness of TIV in preventing laboratory confirmed influenza and the influenza-like illnesses (ILI) in patients with AL.…”