Discussion
Vaccination in oncology patients is typically limited to diseases that are highly prevalent with high risk for morbidity and mortality. This is largely because we know that efficacy of vaccination in immunocompromised patients is poor.1 The analysis of our pediatric oncology cohort, albeit small, reiterates the findings seen in pediatric and adult oncology and transplant patients. Specifically, our cohort showed an inadequate immune response to SARS-COV2 vaccination compared to healthy controls. There was a notable difference between B cell response and T cell response, with less patients having an adequate B cell response. No patients received targeted B cell directed therapy, but we do not have lymphocyte subset data to quantitate B vs T lymphocytes. Another limiting factor is our ability to only complete the T cell assay once, which may impact the validity of that data compared to the B cell data which was repeated multiple times. Lastly, while no patients received steroids during within one week of SARS-COV2 vaccination, many of them had steroids in that phase of therapy, which may have had a greater impact on T cell immunity.12
While previous studies have demonstrated worse immune response in patients with leukemia/lymphoma as compared to solid tumor malignancy,4–7 our numbers were too small to detect differences between these two cohorts. Similarly, we did not find significant differences in immune response based on ALC or degree of myelosuppressive therapy, suggesting that ALC or phase of therapy may not be useful in guiding timing of vaccination or boosters.
There were two other studies to date that have also looked at immunity after SARS-COV2 vaccination in pediatric oncology patients. Both of these studies were from European countries, where only the BNT162b2 (Pfizer) vaccine was available. One study out of Germany included 21 pediatric oncology patients after receiving three doses (the two dose series and a booster).4 The majority of these patients elicited both B and T cell immunity, which was stronger in patients with a solid tumor malignancy and in maintenance phase of therapy. The other study by a group in the Netherlands analyzed 73 patients who received either 2 or 3 doses and also included patients who received a hematopoietic stem cell transplant or CAR T-cell therapy.3 This study demonstrated that time between last treatment and start of the vaccination series impacted immunity, with improved vaccination response in patients who were > 6 weeks from last treatment. Similar to the German study, they showed that three dose series was effective in increasing the humoral immune response. There are a few key differences between these studies and ours. First, there are differences in treatment regimens between North America and Europe that may impact immune response during therapy. Additionally, these other two studies did not include healthy patients as a control, but rather used cutoffs defined by the assays to determine response. Lastly, all of our patients only received a two vaccine series, with very few patients receiving boosters. Our data, taken in context of these other two studies, reiterate the value of booster shots in immunocompromised patients.
The major limitation of our study is a small cohort size, which impacted our ability to analyze how different clinical factors may impact response. Similarly, our minimal enrollment of patients with solid tumor malignancy did not allow us to assess how different malignancies may impact response to vaccination. The Children’s Oncology Group has a study currently open to evaluate immunologic response to COVID-19 vaccination in pediatric oncology patients. This study should shed additional light on how immunocompromised children responds to vaccination, what factors may impact that response, and most importantly, how we should counsel our patients and families regarding risks of infection, importance and timing of boosters, and risk for serious sequelae.