Jane N. Winter, MD

Catherine Bollard, MBChB, MD

Offering their thoughts on the study by Williams et al from the St. Jude Lifetime Cohort were Jane N. Winter, MD, Immediate Past President of the American Society of Hematology (ASH), and Catherine Bollard, MBChB, MD. Both moderated press briefings where the results were presented or discussed. Dr. Winter is Professor of Medicine at the Feinberg School of Medicine, Northwestern University, Chicago. Dr. Bollard is Director of the Center for Cancer & Immunology Research, Professor of Pediatrics, and Attending Physician at Children’s National Hospital and The George Washington University, Washington, DC.

“The treatment of Hodgkin lymphoma is one of hematology’s great success stories, with the vast majority of our patients cured by current therapies,” said Dr. Winter. “But despite trends to reduce the intensity of therapy and the use of radiotherapy in our treatment regimens, long-term survivors are at significant risk of heart and lung toxicities, second malignancies, and also cognitive impairment and premature mortality.”

“The investigators of this study found that survivors of childhood Hodgkin lymphoma showed evidence of epigenetic accelerated aging, based on the study of peripheral blood mononuclear cells. These findings also showed that early epigenetic aging was associated with significant neurocognitive deficits,” she said.

This topic has long been important to Dr. Winter, who has devoted much of her career to advocating for less intensive and less toxic treatments. “We have been aware of the long-term consequences of mediastinal radiation including breast cancer and cardiac issues, but now Dr. Williams and colleagues are shedding light on the neurocognitive deficits I think are underappreciated. We are talking about a population of patients we can cure, only to see them develop neurocognitive deficits later. Being able to screen for this effect of our treatment and perhaps develop strategies to prevent it or deal with it will have wide applicability. If we can get away with it, let’s do less,” proposed Dr. Winter.

Change in Practice Needed in Pediatrics

Dr. Bollard echoed Dr. Winters’ concerns about overtreatment of childhood Hodgkin lymphoma. “We are still giving combined radiation and chemotherapy to the majority of children with more advanced disease, and that is not what is happening in the treatment of adult Hodgkin lymphoma,” she noted.

“I would assert that, hopefully, we as pediatricians do change practice because these combination chemoradiation approaches do have this sort of ‘buildup’ of effects that could affect epigenetic age acceleration. With more immune-based therapies now available, in the future we may not even need radiation or chemotherapy. In 20 years, if we change our treatment practices, maybe these late adverse effects will no longer be seen,” Dr. Bollard concluded. 

DISCLOSURE: Dr. Winter has received research funding and honoraria from Merck. Her spouse has served on data and safety monitoring boards for Ariad, Takeda, Epizyme, and Novartis; and has served as a consultant to Novartis, CVS Caremark, Agios, Gilead, Janssen, and Actinium Pharma. Dr. Bollard is a scientific cofounder and scientific advisory board member for Catamaran Bio and Mana Therapeutics; serves on the Board of Directors of Cabaletta Bio; owns stock in NexImmune and Repertoire Immune Medicine; serves on the data and safety monitoring board for Sobi; and has served as a consultant to BMS, Pfizer, Roche, and Neogene Therapeutics.