Children treated for the most common childhood cancer may lose some protection against measles and chickenpox after completing routine vaccinations, according to new research that could strengthen the case for revaccination following completion of chemotherapy.

Findings published in the journal Pediatrics showed that children who had undergone chemotherapy to treat acute lymphoblastic leukemia (ALL) had lower levels of vaccine-induced immunity against measles and chickenpox than healthy children.

“The study provides proof of concept that additional vaccine doses may be needed, however when, how many doses, and the vaccine effectiveness of additional doses would require further study,” said Monica Ardura, DO, MSCS, chief of the Section of Infectious Diseases at Nationwide Children’s Hospital in Columbus, Ohio, who was not involved in the study. “The study highlights the critical need for more robust clinical vaccine studies that include immunocompromised individuals.”

ALL is the most common type of pediatric cancer, affecting approximately 3100 children and teens in the US annually, and occurs most frequently in children aged 2-5 years. The survival rates are also high, estimated at 80%. The fast-growing malignancy begins in the bone marrow and affects the white blood cells, causing them to multiply and disrupt the production of healthy blood cells.

Chemotherapy can damage immune cells that normally help preserve long-term protection from vaccines, potentially reducing antibody levels built up through childhood immunizations.

Guidelines from the American Academy of Pediatrics and the Infectious Diseases Society of America recommend children with cancer receive the measles, mumps, and rubella and varicella vaccines at least 4 weeks before beginning chemotherapy whenever possible. Because these are live vaccines, they are generally deferred during treatment.

Despite the recommendations, little evidence exists to inform whether children who were previously immunized remain protected after they complete chemotherapy, or whether testing for antibodies is a reliable approach to understanding a patient's level of protection against the infections, Ardura said.

“These remain important questions, especially given the increasing number of measles outbreaks reported both in the United States and globally,” Ardura said.

The study included 45 children aged 2-18 years with ALL who were in the maintenance phase of chemotherapy, within 2 years of completing treatment, or at least 6 months removed from receiving chimeric antigen receptor T-cell therapy. Researchers measured levels of anti-measles and anti-varicella antibodies and compared them with levels found in healthy controls (n = 13).

Investigators found that as the children with ALL aged, antibody levels declined. Patients aged 10-17 years who had received two vaccine doses had significantly lower antibody levels than children aged 6-9 years who received the same doses. Older children also had lower antibody levels than children aged 3-6 years who had received only a single dose.

Although antibody levels were low among patients, the study found that T-cell responses were comparable to those of healthy children, suggesting they retained an important immune mechanism for recognizing and responding to infection.

“We do think that the study tells us that these children should be revaccinated after the completion of therapy,” to restore protection against measles and chickenpox, said Tania Watts, PhD, professor of immunology at the University of Toronto in Toronto, Ontario, Canada, who worked on the study.

Watts noted the study was not designed to determine whether lower antibody levels translated into a higher risk for infection.

But the findings do raise questions about whether guidelines should consider revaccination for immunocompromised children who may lose vaccine-derived immunity.

Clinicians should remain aware of the higher risk for infection that patients with cancer and cancer survivors face and take appropriate steps to mitigate those risks, said Lia Gore, MD, head of hematology/oncology and bone marrow transplantation at Children’s Hospital Colorado in Aurora.

“These data suggest that further study of the immune ‘capacity’ of survivors of childhood ALL should be examined more closely,” said Gore, who was not involved in the study. “It also suggests that other patients treated for childhood cancer could be at similar risk.”

The study was funded by a grant from the Public Health Agency of Canada’s COVID-19 Immunity Task Force. The study authors reported no relevant financial relationships.

Steven Ross Johnson is a journalist who covers public health and healthcare delivery issues.