Survivors of Pediatric HL May Age More Quickly

An analysis of long-term survivors of pediatric Hodgkin lymphoma (HL) revealed an increased risk for cognitive impairment and early death when compared with individuals who never had the disease. The findings, which were recently presented at the 2022 American Society of Hematology Annual Meeting and Exposition in New Orleans, LA, suggest that adults who survived the disease may experience accelerated aging.

While chronologic age remains the same, the pace of biologic, physiologic, and cognitive aging differs greatly among individuals. AnnaLynn Williams, PhD, MS, of Wilmot Cancer Institute in Rochester, NY, said that lifestyle, environmental exposures, and stress play a role. However, researchers hypothesize that a cancer diagnosis and treatment can set people on a trajectory for more rapid aging, known as epigenetic age acceleration (EAA), the gap between epigenetic and chronologic age. EAA depletes physiologic and cognitive reserves—possibly leading to impairment and early death.

“This is an important biomarker in our survivors because they are treated while they still are in physical development and then have a whole life to have all of these other exposures and accumulate more and more damage,” she said.

Researchers turned to St. Jude LIFE, a cohort that follows long-term survivors of childhood cancer throughout adulthood. They compared 215 survivors of pediatric HL of European ancestry who were, on average, 39 years old and 25 years past diagnosis with a control cohort of 282 individuals with an average age of 36. All had undergone a comprehensive neuropsychological battery of tests and provided a blood sample to assess DNA methylation, which changes DNA activity and is associated with aging. DNA methylation is used to calculate EAA.

“If we use computers as an analogy, you can think of your DNA as the hardware and DNA methylation as the software,” said Williams.

Researchers found that pediatric HL survivors had greater EAA versus individuals in the control cohort, with the average difference being 7.7 years. The analysis also showed that higher EAA was associated with worse visual-motor processing speed, short- and long-term memory, and verbal fluency. However, these findings also present an opportunity for early interventions, such as greater attention to physical activity, a healthy diet, and intellectual stimulation, which might improve cognitive function.

“Our hope is that this marker will help us identify those survivors who are most at risk for a neurocognitive impairment so that we might intervene. … In that vein, this marker may help us gauge preclinical response to interventions so that we can demonstrate efficacy earlier than some other endpoints,” said Williams.

Williams also said that an analysis is underway of the full St. Jude LIFE cohort to see whether EAA differs across cancer types.

Jamie Flerlage, MD, MS, of St. Jude Children's Research Hospital in Memphis, TN, noted that the treatment for pediatric HL is significantly shorter than for other cancer childhood cancers, such as leukemia, and therapy does not target the central nervous system, so examining other cancers will be helpful to better understanding EAA. She also said the questions this research raises about the effect of cancer on aging also highlight why EAA should be monitored much earlier.

“I think the next step is to try to really see the timeframe for which these cognitive impairments developed to see what we can do about it to actively try to minimize these late effects that we are now seeing,” said Flerlage. –Aaron Tallent

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