Children who receive hematopoietic stem cell transplants (HSCT) are at high risk for illness and death from influenza infections. Data recently published in The New England Journal of Medicine suggest that a high-dose trivalent influenza vaccine (HD-TIV) offers better protection to this vulnerable population than a standard-dose quadrivalent influenza vaccine (SD-QIV).
Two doses of HD-TIV were associated with significantly higher adjusted geometric mean titers (AGMT) for two specific influenza antigens that both vaccines shared A/H1N1 (adjusted geometric mean ratio [AGMR] 1.65; 95% CI, 1.06 – 2.57; P = .03) and A/H3N2 (AGMR 2.11; 95% CI, 1.32 – 3.38; P = .002), as well as numerically higher titers for B/Victoria-Antigen (AGMR 1.46; 95% CI, 0.93 – 2.31; P = .10), the third antigen in common among the vaccines in the study.
Dr Natasha Halasa
“The allogeneic stem cell transplant population, especially within the first year posttransplant, is one of the most immune-suppressed populations, therefore placing them at high risk for infectious diseases,” Natasha Halasa, MD, MPH, professor of pediatric infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee, told Medscape Medical News. “Many factors that contribute to the development of infections include underlying disease, donor graft source, and conditioning regimen. Also, these factors make them less likely to respond to standard vaccine doses. And, if they do respond, their response is definitely less robust than that of healthy controls.”
The Pediatric HCT Flu Study was conducted over three flu seasons (2016 through 2019) and included 170 participants who were randomly assigned to receive two vaccine doses of either HD-TIV (85 recipients) or SD-QIV (median age 10.9 years, 45% female, with a median time between transplant and enrollment of 7.8 months. Each of two vaccine doses were spaced 28 to 42 days apart.
All participants had hemagglutination-inhibition (HAI) titers measured to all four vaccine- specific influenza antigens (A/H1N1, A/H3N2, B/Victoria, and B/Yamagata) before each vaccine dose and 28 to 42 days after the second dose.
Dr Cameron Wolfe
“There’s a good history of correlating the antibody response (geometric mean titer) to a flu vaccine with expected clinical protection. So a statistically higher level of antibodies to both sub-strains of influenza A (the more severe form, typically) is a strong result. Likewise, numerically higher influenza B antibody titer is also good. These were robust results from a complicated study of very high risk individuals,” explained Cameron R. Wolfe, MBBS, associate professor of medicine at Duke University Medical Center, Durham, North Carolina, who was not associated with the study.
“Our research showed that two doses of HD-TIV is superior to two doses of a SD-QIV for pediatric HCT patients, said Halasa. “The increase in adverse events in HD-TIV recipients was limited to mild or moderate reactions, and all resolved by 3 days after injection.”
The frequency of severe reactions was 7.5% with HD-TIV and 6.0% with SD-QIV after dose 1 and 7.6% with HD-TIV and 6.4% with SD-QIV after dose 2. Injection site reactions and systemic adverse events were assessed for 7 days after dose administration.
Halasa also noted that in order to reach their enrollment goal, the study’s duration was over three flu seasons. This could be seen as a limitation, but “these differences were taken into account in the study’s statistical analysis.” Their study is the largest influenza vaccine trial in a stem cell population, which is a strength.
Nonetheless, an important limitation of the study was that children aged younger than 3 years were not included and the conclusions drawn from its results were limited to HCT patients 3-17 years of age.
N Engl J Med. Published online January 26, 2023. Correspondence
Halasa has received grant funding from Sanofi and Quidel in the past and currently has an investigator-initiated grant from Merck. Wolfe reported no relevant financial relationships.
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