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Neurocognitive Function, Sleep, and Fatigue in Female Childhood ALL Survivors

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:  Neurocognitive Function, Sleep, and Fatigue in Female Childhood ALL Survivors

THE RESEARCH: Cancer: Impact of sleep, fatigue, and systemic inflammation on neurocognitive and behavioral outcomes in long-term survivors of childhood acute lymphoblastic leukemia. Researchers at St. Jude Children’s Research Hospital compiled cohorts of 35 male and 35 female survivors of childhood acute lymphoblastic leukemia with a mean age of 14.3 years and a mean years from diagnosis of 7.4 years. These cohorts were then evaluated with neurocognitive testing, behavioral ratings, reported sleep quality and fatigue symptoms. Additionally, serum markers of systemic inflammation were collected and evaluated. These included, interleukin 1-beta, interleukin-6, tumor necrosis factor alpha, and C-reactive protein.

KEY FINDINGS:  Across the board, survivors performed worse than established population norms on testing evaluating executive functioning and processing speed. Survivors additionally reported more behavioral problems. In female survivors, level of fatigue exacerbated deficits in executive functioning, processing speed, and attention. For female survivors that reported frequent nighttime awakening, there was a correlation with increased inattention hyperactivity, and aggression. Finally, in female survivors impaired executive functioning, processing speed and behavioral problems were correlated with higher levels of interleukin-6, interleukin-1 beta, and C-reactive protein. In contrast, male survivors that had elevated serum levels of tumor necrosis factor alpha demonstrated impaired organization, but no significant link between neurocognitive outcomes and sleep/fatigue was observed.

WHAT THIS MEANS FOR CHILDHOOD CANCER SURVIVORS:  There is a growing body of evidence that therapies directed at preventing central nervous system (CNS) relapse of leukemia (chemotherapy injected into the CNS and craniospinal radiation) are associated with impairments in neurocognitive function. There is also emerging evidence that systemic chemotherapy can also impair cognitive function. The concept of “chemo brain” is not new, but with advances in neuroscience developing in basic science labs around the world, the ability of the oncology community to begin to understand what drives these symptoms is becoming increasingly feasible. This study included a relatively small number of ALL survivors, but demonstrates the negative aspects of successful ALL therapy with respect to neurocognitive outcomes. Moreover, the distinct differences in the female group and the links between systemic inflammatory markers and worse neurocognitive function highlights the need to better understand how pediatric chemotherapy exposure impacts development and overall health. Elucidating the mechanisms of how impaired development caused by early chemotherapy exposure impacts brain health is crucial to improving long-term outcomes for these patients. For all survivors, this study indicates that follow-up monitoring for school, sleep, and behavioral difficulties is essential. Parents and survivors should remain vigilant in monitoring for these symptoms. Meanwhile, the scientific community must seek to understand the basic mechanisms that drive differences in neurocognitive outcomes as they relate to sex and underlying inflammatory status.




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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One Response to Neurocognitive Function, Sleep, and Fatigue in Female Childhood ALL Survivors

  1. Pingback: New Biomarker Predicts Late Neurocognitive Deficits in Adult Survivors of Childhood Leukemia - Cancer Knowledge Network

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