Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants

Schuster, Jennifer E; Hamdan, Lubna; Dulek, Daniel E.; Kitko, Carrie L.; Batarseh, Einas; Haddadin, Zaid; Stewart, Laura S; Stahl, Anna L; Potter, Molly; Rahman, Herdi; Kalams, Spyros A.; Coffin, Susan; Ardura, Monica I.; Wattier, Rachel L.; Marón, Gabriela; Bocchini, Claire; Moulton, Elizabeth A; Grimley, Michael; Paulsen, Grant; Harrison, Christopher J.; Freedman, Jason L.; Carpenter, Paul A.; Englund, Janet A.; Muñoz, Flor M.; Danziger‐Isakov, Lara; Spieker, Andrew J.; Halasa, Natasha

doi:10.1056/nejmc2210825

Cited by 15 publications

(14 citation statements)

References 4 publications

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“…The samples for this study were isolated from pediatric HCT recipients who were aged 3 to 17 years, and 3 to 35 months after allogeneic HCT at the time of enrollment in a phase 2, multicenter, double-blinded, randomized controlled trial ( www.clinicaltrials.gov identifier: NCT02860039) comparing 2 doses of HD-TIV with 2 doses of SD-QIV at 9 US study sites over 3 consecutive influenza seasons (2016-2017, 2017-2018, and 2018-2019). 13 , 14 Each study participant was randomized to receive 2, 0.5 mL intramuscular doses of either HD-TIV or SD-QIV with a target interval of 28 to 42 days between vaccine doses (at the time of this study, the HD formulation of the quadrivalent vaccine was not available). Blood collection for serum and peripheral blood mononuclear cells (PBMCs) was performed on the day of the first vaccination, 28 to 42 days after the second vaccination (to estimate peak immunogenicity), and ∼6 months after the second vaccination (to estimate sustained immunogenicity).…”

Section: Methodsmentioning

confidence: 99%

“… 5 , 6 , 7 , 8 One approach to improve response is to administer high-dose inactivated influenza vaccines. 9 , 10 , 11 , 12 , 13 , 14 In our recent multicenter, randomized controlled trial, a 2-dose series of high-dose trivalent influenza vaccine (HD-TIV) was associated with significantly higher geometric mean hemagglutinin inhibition (HAI) titers against influenza A/H3N2 and A/H1N1 compared with 2 doses of standard-dose quadrivalent influenza vaccine (SD-QIV) in pediatric HCT recipients, 3 to 35 months after transplant. 13 , 14 …”

Section: Introductionmentioning

confidence: 99%

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Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients

Amarin,

Dulek,

Simmons

et al. 2024

Blood Advances

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Pediatric hematopoietic cell transplant (HCT) recipients exhibit poor serologic responses to influenza vaccination early after transplant. To facilitate the optimization of influenza vaccination timing, we sought to identify B and T cell subpopulations associated with influenza vaccine immunogenicity in this population. We used mass cytometry to phenotype peripheral blood mononuclear cells (PBMCs) collected from pediatric HCT recipients enrolled in a multicenter influenza vaccine trial comparing high- and standard-dose formulations over three influenza seasons (2016-2019). We fit linear regression models to estimate relationships between immune cell subpopulation numbers before vaccination and pre- to post-vaccination geometric mean fold-rises in antigen-specific (A/H3N2, A/H1N1, and B/Victoria) serum hemagglutination-inhibition antibody titers (28-42 days and approximately 6 months after two doses). For cell subpopulations identified as predictive of a response to all three antigens, we conducted a sensitivity analysis including time post-transplant as an additional covariate. Among 156 HCT recipients, we identified 33 distinct immune cell subpopulations. Seven significantly predicted responses to all three antigens 28-42 days after a two-dose vaccine series, irrespective of vaccine dose. We also found evidence that baseline absolute numbers of naïve B cells, naïve CD4+ T cells, and circulating T follicular helper cells predicted peak and sustained vaccine-induced titers irrespective of dose or timing of post-transplant vaccine administration. In conclusion, several B and T cell subpopulations predicted influenza vaccine immunogenicity in pediatric HCT recipients. This study provides insights into the immune determinants of vaccine responses and may help guide the development of tailored vaccination strategies for this vulnerable population.-

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients

Amarin,

Dulek,

Simmons

et al. 2024

Blood Advances

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“…44 Two high-dose IIV doses were safe and showed superior immunogenicity for influenza A antigens compared to standard dose in pediatric HSCT recipients ages 3-17 years. 150 Clinical interpretation. The high-dose influenza vaccine is safe and has improved immunogenicity compared to the standard-dose vaccine.…”

Section: Influenza Vaccinesmentioning

confidence: 99%

“…44 Two high-dose IIV doses were safe and showed superior immunogenicity for influenza A antigens compared to standard dose in pediatric HSCT recipients ages 3-17 years. 150…”

Section: Clinical Question 2: What Additional Vaccinations and Revacc...mentioning

confidence: 99%

Vaccination of Adults With Cancer: ASCO Guideline

Kamboj,

Bohlke,

Baptiste

et al. 2024

JCO

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ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by providers and should be used in conjunction with independent professional judgment. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature, and is not intended as a statement of the standard of care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and Appendix 2 (online only) for more. PURPOSE To guide the vaccination of adults with solid tumors or hematologic malignancies. METHODS A systematic literature review identified systematic reviews, randomized controlled trials (RCTs), and nonrandomized studies on the efficacy and safety of vaccines used by adults with cancer or their household contacts. This review builds on a 2013 guideline by the Infectious Disease Society of America. PubMed and the Cochrane Library were searched from January 1, 2013, to February 16, 2023. ASCO convened an Expert Panel to review the evidence and formulate recommendations. RESULTS A total of 102 publications were included in the systematic review: 24 systematic reviews, 14 RCTs, and 64 nonrandomized studies. The largest body of evidence addressed COVID-19 vaccines. RECOMMENDATIONS The goal of vaccination is to limit the severity of infection and prevent infection where feasible. Optimizing vaccination status should be considered a key element in the care of patients with cancer. This approach includes the documentation of vaccination status at the time of the first patient visit; timely provision of recommended vaccines; and appropriate revaccination after hematopoietic stem-cell transplantation, chimeric antigen receptor T-cell therapy, or B-cell–depleting therapy. Active interaction and coordination among healthcare providers, including primary care practitioners, pharmacists, and nursing team members, are needed. Vaccination of household contacts will enhance protection for patients with cancer. Some vaccination and revaccination plans for patients with cancer may be affected by the underlying immune status and the anticancer therapy received. As a result, vaccine strategies may differ from the vaccine recommendations for the general healthy adult population vaccine. Additional information is available at www.asco.org/supportive-care-guidelines .

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“…Although the response to vaccination is suboptimal in HCT recipients, a prospective observational study demonstrated that vaccination was associated with reduced risk of FLU LRTI [45]. Various vaccine strategies including two-dose, high-dose trivalent inactive FLU vaccination have been reported to be effective [46,47]. FLU vaccination is recommended for not only patients but also households.…”

Section: Risk Factors For Severity In Influenza Virusmentioning

confidence: 99%

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients

Matsui,

Ogimi

2023

Current Opinion in Infectious Diseases

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Purpose of review Seasonal respiratory virus infections (RVIs) often progress to severe diseases in hematopoietic cell transplant (HCT) recipients. This review summarizes the current evidence on risk factors for the severity of RVIs in this high-risk population and provides clinical management. Recent findings The likelihood of the respiratory viral disease progression depends on the immune status of the host and the type of virus. Conventional host factors, such as the immunodeficiency scoring index and the severe immunodeficiency criteria, have been utilized to estimate the risk of progression to severe disease, including mortality. Recent reports have suggested nonconventional risk factors, such as hyperglycemia, hypoalbuminemia, prior use of antibiotics with broad anaerobic activity, posttransplant cyclophosphamide, and pulmonary impairment after RVIs. Identifying novel and modifiable risk factors is important with the advances of novel therapeutic and preventive interventions for RVIs. Summary Validation of recently identified risk factors for severe RVIs in HCT recipients is required. The development of innovative interventions along with appropriate risk stratification is critical to improve outcomes in this vulnerable population.

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Influenza Vaccine in Pediatric Recipients of Hematopoietic-Cell Transplants

Cited by 15 publications

References 4 publications

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients

Immunophenotypic predictors of influenza vaccine immunogenicity in pediatric hematopoietic cell transplant recipients

Vaccination of Adults With Cancer: ASCO Guideline

Risk factors for severity in seasonal respiratory viral infections and how they guide management in hematopoietic cell transplant recipients

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