Although most children and adolescents with cancer have mild illness from COVID-19 infection, some do experience severe disease and a small percentage even die, according to a recent analysis.
“We wanted to create a global pool of evidence to answer the question: Do we see severe [COVID-19] infection [in children with cancer]?” corresponding author Sheena Mukkada, MD, St. Jude Children’s Research Hospital, Memphis, Tennessee, told Medscape Medical News.
In a cohort of 1319 pediatric patients followed for 30 days, Mukkada and colleagues reported that 80% of these patients had asymptomatic to moderate disease from COVID-19, while 1 in 5 experienced severe or critical illness and almost 4% died — four times the mortality rate observed in published cohorts of general pediatric patients.
The results highlight that “children and adolescents with cancer generally recover without incident from COVID-19, but can have a severe course of infection,” the authors concluded.
And knowing that some children can get very sick, investigators wanted “to identify who these patients are so that we can prioritize and protect that group,” she added.
Echoing that sentiment, Kathy Pritchard-Jones, MD, president of the International Society of Paediatric Oncology (SIOP) and co-author on the study, noted in a press release that “by working together to create this global registry, we have enabled hospitals around the world to rapidly share and learn how COVID-19 is affecting children with cancer.”
Pritchard-Jones commented that overall these results provide reassurance that “many children can continue their cancer treatment safely, but they also highlight important clinical features that may predict a more severe clinical course and the need for greater vigilance for some patients.”
Inside the Global Registry Data
The Global Registry of COVID-19 in Childhood Cancer, created jointly by St. Jude Children’s Research Hospital and SIOP, included data from 131 institutions in 45 countries. Children recruited into the registry between April 2020 and February 2021 ranged in age from infancy to 18 years old.
Most patients remained asymptomatic (35%) or experienced mild to moderate illness (45%), though 20% did develop severe or critical illness.
The investigators highlighted several factors associated with a greater risk of developing more severe illness from COVID-19, which included cancer type, intensity of therapy, age, absolute lymphocyte count, and presence of comorbidities or COVID-19 symptoms.
Notably, more than 80% of either severe or critical infections occurred in patients with hematological malignancies — with 56% of cases in patients with acute lymphoblastic lymphoma or acute lymphoblastic leukemia — followed by extracranial solid tumors (15.8%), and central nervous system tumors (2.7%).
In patients with acute lymphoblastic leukemia or acute lymphoblastic lymphoma, severe or critical disease was most common in those receiving induction therapy (30%), relapse or refractory therapy (30%), and those in the maintenance or continuation phase of therapy (19%).
Older age was associated with a higher likelihood of having severe disease — with the lowest risk in infants (9.7%) and the highest in the 15- to 18-year-old cohort (27.3%).
Patients with lymphopenia who had an absolute lymphocyte count of 300 cells per mm3 or less and an absolute neutrophil count of 500 cells per mm3 or more also had an elevated risk of severe illness from COVID-19.
Regarding whether the presence of lymphopenia or neutropenia should change the treatment approach, Mukkada noted that, when possible, these patients should receive antiviral treatment, such as remdesivir, if the center has antivirals, or be prioritized for hospital admission.
Modifying cancer treatment might be recommended if patients are highly lymphopenic or have very low neutrophil counts, but a more effective strategy is simply to ensure that age-eligible children and adolescents with cancer or who have had a hematopoietic stem-cell transplantation have been fully vaccinated against COVID-19. For children who are not yet age-eligible, everyone around them should be vaccinated.
Pediatric patients in low- and middle-income countries were also more likely to have severe or critical outcomes from COVID-19 (41.7%) compared with patients in other income groups (23.9%).
The impact of COVID-19 “has been felt in every corner of the world, but particularly in low- and middle-income countries compared to high-income countries,” senior author Carlos Rodriguez-Galindo, MD, global director at St. Jude, said in a statement.
In terms of the intersection of cancer treatment and COVID diagnosis, almost 83% of pediatric patients were receiving treatment for their cancer. Chemotherapy was withheld in about 45% of these patients and some modification to the treatment regimen occurred in almost 56% of participants on active therapy.
“Treatment modifications were least common in patients from upper-middle income countries compared with other income groups,” the authors write.
Although an interesting observation, Mukkada noted that the registry data could not explain why treatment modifications occurred less frequently in upper-middle income countries as opposed to high-income and lower-income countries.
UK Monitoring Project
Not all studies, however, have found that COVID-19 infection is significantly more severe in children with cancer. In a 2020 report from the UK Paediatric Coronavirus Cancer Monitoring Project, researchers evaluated all children in the United Kingdom under the age of 16 diagnosed with COVID and cancer.
“[Given that] we had complete coverage of every center in the UK that cares for children with cancer, we are confident that we picked up at least all the severe or critical cases,” lead author Gerard Millen, MD, honorary clinical research fellow, University of Birmingham, Birmingham, UK, said in an email to Medscape Medical News.
Between March 2020 and July 2020, Millen and colleagues identified 54 positive cases of COVID-19, 15 (28%) of which were asymptomatic, 34 (63%) mild, and 4 (7.4%) severe or critical — more in line with the incidence of severe illness reported in the general pediatric population.
“Thankfully, we had no children with cancer in the UK who died from COVID-19,” Millen noted. “Overall, in the UK, we have taken the approach that the majority of children with cancer in this country are at very low risk from COVID-19 and that we do not have good evidence to modify their treatment.”
Millen pointed out that the data in the UK study were “remarkably similar” to those from the high-income countries in the global St Jude/SIOP cohort, where 7.4% of patients in that cohort had severe or critical disease compared with 7.4% of patients from their own UK cohort.
“I think many of the key differences between the two cohorts reflect the fact that access to treatment in many low-to-middle income countries is more challenging with many factors contributing to overall poorer outcomes for both cancer and noncancer metrics,” Millen said.
Both the UK and registry studies were performed prior to vaccinations becoming available to older children, and before the emergence of certain variants, including the Delta variant, which is responsible for the most recent surge of COVID-19 infections around the world.
Data on COVID-19 vaccination in children with cancer are limited but promising so far.
As for whether the Delta variant might affect outcomes for children with cancer and COVID-19, Mukkada could only speculate, but she noted “what we are hearing anecdotally about the [Delta] disease being more severe, even in patients who don’t have cancer, is leading us to say that we can’t close the registry yet. We are still actively enrolling children.”
The study was funded by the American Lebanese Syrian Associated Charities and the National Cancer Institute. The study authors and Dr Millen have disclosed no relevant financial relationships.
Lancet Oncology. Published online August 26, 2021. Full text