The Centers for Disease Control and Prevention (CDC) recommends annual, age-appropriate inactivated or recombinant influenza vaccination for immunocompromised patients, noting that immune responses may be reduced with post-transplant regimens. However, the CDC does not specifically recommend standard- versus high-dose vaccination for pediatric immunocompromised patients, address pediatric hematopoietic stem cell transplant (HSCT) recipients, or provide guidance on high-dose vaccination in subsequent post-transplant seasons. [1]
The latest National Comprehensive Cancer Network (NCCN) guidelines on the prevention and treatment of cancer-related infections (Version 1.2026) recommend annual injectable influenza vaccination beginning 3-6 months after hematopoietic cell transplant, with consideration of a high-dose vaccine or re-dose. Patients with hematologic or solid tumor malignancy should receive an inactivated or recombinant influenza vaccine. However, the guideline does not provide pediatric-specific recommendations for high-dose vaccination or specific guidance on high-dose use in subsequent post-transplant seasons. [2]
The 2024 American Society of Clinical Oncology (ASCO) guideline on vaccination of adults with cancer recommends high-dose inactivated influenza vaccine (IIV) for adult HSCT recipients regardless of age, based on improved immunogenicity compared with standard-dose IIV. Influenza vaccination is generally administered 6 months after HSCT but may be given 3-6 months after autologous or allogeneic HSCT during periods of high community transmission. A randomized trial in pediatric HSCT recipients aged 3-17 years found 2 doses of high-dose IIV were safe and demonstrated superior immunogenicity for influenza A antigens compared with standard-dose IIV (Table 1). However, the guideline is specifically intended for adults with cancer, does not provide a pediatric-specific high-dose recommendation, and does not address high-dose vaccination in subsequent influenza seasons after the initial post-transplant season. They also do not make a recommendation of 2 doses versus a single dose. [3]
The 2025 Infectious Diseases Society of America (IDSA) guidelines on the use of vaccines for the prevention of seasonal COVID-19, influenza, and RSV Infections in immunocompromised patients note that high-dose or adjuvanted influenza vaccines produce more robust immune responses, which may be particularly important in immunocompromised patients. Similarly, this guidance does not specifically address pediatric HSCT recipients or provide recommendations for high-dose vaccination in subsequent post-transplant influenza seasons. [4]
A 2026 American Academy of Pediatrics (AAP) review article discussing influenza vaccination in immunocompromised children highlights a phase 2 multicenter randomized controlled trial in pediatric allogeneic HCT recipients (Pediatric HCT Flu Study) in which 2 doses of high-dose inactivated influenza vaccine were more immunogenic than 2 doses of standard-dose vaccine when administered 3-35 months after HCT, with similar safety (see Table 1). Based on these data, the authors suggest that clinicians may consider 2 doses of HD-IIV in HCT recipients ≥3 years of age during the first post-transplant influenza season; however, HD-IIV is not currently approved for pediatric use. The authors also note that a subset of patients from the phase 2 study reenrolled the following year, with results suggesting that 1 dose of either high- or standard-dose vaccine may be sufficient in the subsequent season if 2 HD-IIV doses were received during the first post-transplant vaccine season (see Table 2). The review further notes that these data are based on small studies and that more comprehensive clinical studies of alternative influenza vaccine formulations and dosing strategies in pediatric patients are needed. [5]
A 2025 systematic review and meta-analysis evaluated high-dose versus standard-dose influenza vaccination after HCT across 4 randomized controlled trials (n= 402), including both adult and pediatric recipients. Only 1 of the 4 included randomized controlled trials specifically evaluated pediatric HCT recipients, representing the same phase 2 trial briefly described in the Kao et al., review; this trial included children with a mean age of approximately 11 years who were vaccinated either 3-5 months or 6-35 months after HCT (see Table 1). The overall findings from the meta-analysis suggested that high-dose vaccination did not significantly improve hemagglutination inhibition titers ≥1:40 after the first dose, second dose, or at 6 months, although the >4-fold antibody response favored high-dose vaccination after the second dose (odds ratio [OR] 1.29; 95% CI 1.00 to 1.66; p= 0.05). There was no significant difference in confirmed influenza (OR 1.61; 95% CI 0.67 to 3.87), while local adverse effects were more frequent with high-dose vaccination (42.3% vs. 16.8%); systemic adverse effects did not significantly differ. The analysis did not specifically evaluate high-dose vaccination strategies in subsequent post-transplant influenza seasons, although it references the same second-season study described above, in which a subset of pediatric HCT recipients from the original trial were vaccinated during a second consecutive influenza season (see Table 2). [6]