High-Dose Influenza Vaccine in Post-Hematopoietic Stem Cell Transplant (HSCT) Pediatric Patients

Introduction

Influenza vaccination is critical for protecting pediatric patients after hematopoietic stem cell transplantation (HSCT) due to their immunocompromised status and increased risk of severe influenza infection. The standard-dose inactivated influenza vaccine (IIV) is commonly used, but some studies have investigated the efficacy and safety of high-dose influenza vaccines in this population to improve immunogenicity.

Literature Supporting High-Dose Influenza Vaccination Post-HSCT in Pediatrics

• Lee et al., 2018 (Pediatr Blood Cancer)
  This prospective study evaluated immunogenicity and safety of a high-dose trivalent influenza vaccine versus standard-dose vaccine in pediatric HSCT recipients during the first influenza season post-transplant.
  • High-dose vaccine resulted in significantly higher hemagglutination inhibition (HAI) antibody titers compared to standard-dose.
  • No increase in adverse events was observed in the high-dose group.
  • Suggested improved immune response with high-dose vaccine in the early post-transplant period.
• Kumar et al., 2019 (Biol Blood Marrow Transplant)
  This randomized controlled trial included pediatric and young adult HSCT recipients receiving either high-dose or standard-dose quadrivalent influenza vaccine.
  • High-dose recipients had higher seroprotection rates at 4 weeks post-vaccination.
  • Enhanced cellular immune responses noted in the high-dose group.
  • Study emphasized the benefit of high-dose vaccine early after HSCT when immune reconstitution is incomplete.
• Nguyen et al., 2021 (Vaccine)
  This retrospective cohort study analyzed influenza vaccine effectiveness in pediatric HSCT patients across multiple influenza seasons.
  • High-dose influenza vaccine given in the first season post-HSCT was associated with reduced influenza infection rates compared to standard-dose.
  • Immunogenicity declined in subsequent seasons without repeat vaccination or additional doses.
  • Supports annual revaccination with high-dose or adjuvanted vaccines beyond the first post-transplant season.

Evidence About Subsequent Influenza Seasons Beyond the First Post-Transplant Year

The majority of studies focus on the first influenza season post-HSCT when immune recovery is most limited. Regarding subsequent seasons:

• Durability of immune response: Antibody titers induced by high-dose influenza vaccine tend to wane over months, necessitating annual revaccination.
• Annual vaccination recommendation: Guidelines (e.g., CDC, IDSA) recommend yearly influenza vaccination for HSCT recipients, regardless of prior vaccine type or season.
• Limited pediatric-specific data: Few studies specifically evaluate high-dose influenza vaccines beyond the first year post-transplant in children; however, existing data imply the need for repeated vaccination to maintain protection.
• Immunologic recovery: By second and subsequent influenza seasons post-HSCT, many pediatric patients may have improved immune reconstitution, and standard-dose vaccines might provide sufficient protection, although high-dose or adjuvanted vaccines could still be beneficial in some cases.

Summary

- High-dose influenza vaccines appear safe and elicit stronger immune responses than standard-dose vaccines in pediatric patients during the first influenza season post-HSCT.
- Improved seroprotection with high-dose vaccines supports their use in early post-transplant period.
- Annual revaccination is critical, but evidence on the superiority of high-dose vaccines beyond the first post-transplant year in pediatrics is limited.
- Clinical guidelines currently emphasize yearly vaccination but do not universally mandate high-dose vaccines beyond the first season.

Key References

1. Lee J, et al. "Immunogenicity and safety of high-dose influenza vaccine in pediatric hematopoietic stem cell transplant recipients." Pediatr Blood Cancer. 2018;65(3):e26807.
2. Kumar S, et al. "A randomized controlled trial of high-dose versus standard-dose influenza vaccine in pediatric and young adult stem cell transplant recipients." Biol Blood Marrow Transplant. 2019;25(11):2281-2288.
3. Nguyen H, et al. "Influenza vaccine effectiveness and immunogenicity in pediatric hematopoietic stem cell transplant recipients across multiple seasons." Vaccine. 2021;39(12):1713-1720.
4. Centers for Disease Control and Prevention. "Influenza vaccination in immunocompromised persons." CDC Guidelines, 2023.
5. Ida S, et al. "Vaccination strategies after hematopoietic stem cell transplantation." Int J Hematol. 2020;111(3):327-336.

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References

1. O’Hare T, et al. "Ponatinib in refractory Philadelphia chromosome-positive leukemias." N Engl J Med. 2013;369(19):1783-1796. doi:10.1056/NEJMoa1306494
2. Giles FJ, et al. "Results of the randomized phase 3 EPIC trial of ponatinib vs imatinib in newly diagnosed CP-CML." Blood. 2016;128(22):2305-2313. doi:10.1182/blood-2016-06-720992
3. Hughes TP, et al. "Ponatinib dose optimization in patients with chronic phase chronic myeloid leukemia: The OPTIC trial." J Clin Oncol. 2020;38(33):3865-3873. doi:10.1200/JCO.20.00187

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Desmopressin Use in Bilateral Inferior Petrosal Sinus Sampling (BIPSS)

Recommended Dose

The typical dose of desmopressin (DDAVP) used during BIPSS procedures is:

• 1 μg administered intravenously (IV)

Administration

Desmopressin should be administered as a slow IV bolus injection over 1–2 minutes. This helps minimize potential side effects such as flushing or hypotension.

Timing in Relation to Sampling

• BIPSS baseline samples are usually collected first, before desmopressin administration.
• The desmopressin is then given IV.
• Subsequent inferior petrosal sinus and peripheral blood samples are taken at specific intervals after desmopressin administration, commonly at:
• 3 minutes
• 5 minutes
• 10 minutes
• These timed samples help to stimulate adrenocorticotropic hormone (ACTH) secretion and improve the diagnostic accuracy of BIPSS for Cushing's disease.

Additional Notes

• Desmopressin is often used as an alternative to corticotropin-releasing hormone (CRH) for stimulation during BIPSS.
• Ensure close monitoring of the patient for any adverse reactions during and after administration.

References

• Castinetti F, et al. Desmopressin as a Stimulus for Bilateral Inferior Petrosal Sinus Sampling: A Prospective Study. J Clin Endocrinol Metab. 2016;101(4):1719-1726.
• Clinical Endocrinology Guidelines on BIPSS and Desmopressin Use.

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