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New Biomarker Predicts Late Neurocognitive Deficits in Adult Survivors of Childhood Leukemia

GregoryAuneby Gregory Aune, MD, PhD, CKN Editor


Childhood Cancer Survivors have their own unique set of issues that often go unaddressed by health care professionals once treatment has ended and the child enters adulthood.  Although the last 20 years have seen growth in survivorship research, this research is rarely filtered down to the people who need it most – the survivors and their families.  Dr. Gregory Aune, Pediatric Oncologist, researcher, childhood cancer survivor and advocate, has taken on the position of CKN Editor, Knowledge Translation – Childhood Cancer Survivorship.  His goal is simple:  to help empower childhood cancer survivors to start a dialogue with their doctors by publishing short, easy-to-read research study summaries, like this one.


THE HEADLINE:  Childhood Cancer Survivors Who Undergo Chemotherapy May Have Thinking, Memory Problems as Young Adults, Study Suggests

THE RESEARCH: Journal of the National Cancer Institute:  Neurocognitive Sequelae in Adult Childhood Leukemia Survivors Related to Levels of Phosphorylated Tau.  Researchers compared intellectual performance, memory, and executive functioning between 31 long-term adult survivors of childhood leukemia and 35 matched control subjects.  In addition, correlations were evaluated between these cognitive outcomes and prior dose exposures to intrathecal methotrexate and with levels of phosphorylated Tau protein (p-Tau) in cerebrospinal fluid (CSF).

KEY FINDINGS:  CSF levels of p-Tau during treatment and total intrathecal methotrexate dose were both negatively correlated with adult intellectual performance.  Interestingly, long-term memory and attention-control, which both are mature before the survivors mean age of diagnosis, were not affected.  In contrast, cognitive flexibility and information processing, which both mature during adolescence were impaired in the survivors evaluated.  These data establish CSF p-Tau levels during treatment as a potential biomarker for later cognitive deficits.

WHAT THIS MEANS FOR CHILDHOOD CANCER SURVIVORS:  As noted in last week’s post, a large body of evidence has recently emerged that documents the neurocognitive toxicity of chemotherapy and radiation exposure.  This study provides further evidence and additionally identifies p-Tau as a marker, that if elevated in the CSF during treatment, may predict an increased likelihood of developing cognitive deficits.  Tau proteins and their significance in neurodegenerative diseases have been extensively studied.  These proteins are mostly found in neurons and they are known to modulate critical functions that overall promote neuronal health.  Abnormal Tau protein function and accumulation in CSF have been noted in dementia and following traumatic brain injury.  While this study is very early and much is unknown about the underlying mechanisms of chemotherapy-induced damage to brain tissue, it does illustrate the potential benefits for survivors staying actively engaged in long-term follow-up care.  As a better understanding of the impact of these findings is achieved, those survivors with consistent follow-up will be best positioned to receive the medical interventions that will maximize long-term health.  It is critical that further research is conducted to better understand the trajectory of neurocognitive function in all childhood cancer survivors as they progress through the stages of aging.




Medical Disclaimer:  The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images and information, contained on or available through this web site is for general information purposes only.  If you feel the research summarized applies to you or someone you know, talk to your doctor about your concerns.



Videos with Dr. Aune

Presentation on YouTube (Jan 2015):  Eliminating Long-term Health Effects in Cancer Survivors – Gregory Aune, MD, PhD

Interview for the National Coalition for Cancer Survivorship (June 2015):  Hodgkin’s Lymphoma Survivor Dr. Greg Aune Discusses Issues in Long-Term Survivorship Care

Interview with the Washington Post Live Summit (Dec 2016): How cancer lives on in young adults after treatment ends



Dr. Gregory J. Aune is the Stephanie Edlund Distinguished Professor of Pediatric Cancer Research and a St. Baldrick’s Foundation Scholar.  His experience in pediatric cancer spans over 27 years and encompasses his own patient experiences, research in experimental therapeutics, clinical care of pediatric oncology patients, and childhood cancer advocacy.  His interest in pediatric oncology began at age 16, when he was diagnosed with Hodgkin’s lymphoma.  While fortunate to survive, the experiences he encountered as a patient initiated a path towards a research and clinical career aimed at developing less toxic chemotherapy regimens.  His experience as a long-term survivor included open-heart surgery at age 35 to replace his aortic valve and bypass three blocked coronary arteries that were damaged by his teenage cancer therapies.  This life-changing event initiated his research interest in cardiac disease.  His training to become a successful physician scientist and pediatric oncologist has included time spent at some of the most well-respected oncology institutions in the United States including, M.D. Anderson Cancer Center, the National Cancer Institute, and Johns Hopkins Hospital.

Dr. Aune is a national leader in childhood cancer advocacy efforts.  In San Antonio, he has been a leader in local fundraising and awareness efforts.   Since 2010, he has spearheaded efforts by the St. Baldrick’s Foundation and For the Kids Dance Marathon at the University of Texas San Antonio that have raised over $830,000 for childhood cancer patients and research efforts.  In September 2014, his appointment to the National Cancer Institute Council of Research Advocates (NCRA) was announced by NCI Director Dr. Harold Varmus at a White House briefing on childhood cancer.

In addition, Dr. Aune is a policy advisor for the National Coalition for Cancer Survivorship, serves on the Board of Directors of the American Childhood Cancer Organization, is a member of the St. Baldrick’s Foundation National Advocacy Committee, and serves on the scientific advisory board for the Canines-N-Kids foundation.

In May 2015, Dr. Aune addressed the 68th World Health Assembly in Geneva, Switzerland and called on the World Health Organization to make childhood cancer a top global health priority.



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