Teenage girl with short brown hair ready for an MRI.

Teenage patient in hospital gown with a big smile.Arkansas Children’s — the state’s only Children’s Oncology Group (COG) member institution — provides access to the latest clinical trials for children in the region. Two NIH-funded research initiatives aim to improve long-term outcomes for children and teens with acute lymphoblastic leukemia (ALL). One project focuses on early cognitive assessments to identify neurocognitive effects soon after diagnosis. The second evaluates the impact of structured exercise programs on physical function, fatigue and overall quality of life in children undergoing therapy for ALL. These studies reflect Arkansas Children’s commitment to advancing evidence-based supportive care as an essential component of comprehensive pediatric oncology. 

“Identifying Markers of Abnormal Neurocognitive Trajectories during Chemotherapy Treatment of Childhood Acute Lymphoblastic Leukemia” led by Ellen van der Plas, Ph.D., a researcher at Arkansas Children’s Research Institute and associate professor of hematology/oncology at the University of Arkansas for Medical Sciences (UAMS), aims to help leukemia survivors achieve the same quality of life as their peers who have not had cancer by answering the question: “What are the earliest signs of abnormal brain development in children who are newly diagnosed with leukemia?” 

With survival rates for pediatric acute lymphoblastic leukemia approaching 95%, attention is shifting to improving the quality of life of survivors after treatment. Many survivors experience lasting cognitive challenges that interfere with daily life because therapies target the brain. The cause of these cognitive issues remains unclear. 

“Without identifying the earliest signs of brain changes, we cannot design effective strategies to prevent or reduce these problems,” van der Plas said. 

The project has three specific aims: 

  • Identifying changes in discrete components of executive function in pediatric leukemia patients and healthy peers; 
  • Identifying differences in neurodevelopmental changes between leukemia patients and healthy peers; 
  • Examining neurochemical markers of brain injury in cerebrospinal fluid samples in leukemia patients and evaluating their relationship with neurodevelopmental outcomes. 

To achieve these goals, children with and without leukemia, ages 3–10, are assessed three times over the course of a year. During each visit, they complete puzzles and games that measure thinking and planning skills and undergo a non-sedated MRI scan. The MRI uses specialized techniques to capture different aspects of the brain, including its structure, connections, activity and chemical makeup. Analysis of leftover cerebrospinal fluid provides data about protein markers of brain injury. 

“Initial results suggest some mental functions — such as remembering visual and spatial information, thinking flexibly and controlling impulses — are weaker in children with leukemia compared with healthy peers,” van der Plas said. “We also see that the brain’s white matter, especially in the frontal lobes, shows reduced integrity in leukemia patients compared to peers. In addition, early signs of an ‘energy crisis’ are apparent, with certain brain chemicals elevated while others are reduced.” 

The $2.5 million Method to Extend Research in Time (MERIT) award grant provides five years of support with the opportunity for a two-year extension. 

Previous research shows that leukemia survivors, even decades after treatment, often exhibit changes in brain structure, particularly in white matter, and experience cognitive difficulties that can affect school and work performance. Building on this knowledge, this project advances the field by identifying some of the earliest brain and cognitive changes that occur during or shortly after treatment. 

MRI machine.

A related ACRI project funded by the NIH as a K12 Institutional Career Development Program is the “Strength and Outpatient Exercise Regimen in Children with Acute Lymphoblastic Leukemia/Lymphoma (STRONGER ALL)” led by Lauren Appell, M.D., a pediatric oncologist/hematologist at Arkansas Children’s and assistant professor in the department of pediatrics at UAMS. 

The late (those starting after treatment) and long-term (those starting during treatment and continuing after treatment ends) side effects of cancer therapies can affect all organs and systems. Survivors of cancer can experience bowel or bladder problems, mental health issues or skeletal issues. 

The STRONGER ALL project focuses on metabolic syndromes and cardiometabolic disease affected by some cancer treatments. Late-effect conditions include high blood pressure, high blood sugar and unhealthy cholesterol levels. Chemotherapy, radiation and surgery can lead to hormonal imbalances and organ damage, increasing the risk of cardiovascular disease and diabetes. The sedentary lifestyle unintentionally adopted by many patients compounds the risks associated with the treatments. Treatments can be both time-consuming and physically taxing, leading to a decreased desire for physical activity. 

This study examines the impact of incorporating physical exercise into treatment, with the goal of enhancing the quality of life for survivors. It will also add to the body of knowledge regarding the capabilities of patients undergoing treatment. 

“There are no consensus guidelines for what is safe or doable for physical activity for children who are actively receiving chemo for ALL,” Dr. Appell said. 

This interventional study involves monitoring participants, ages 11–21, during 30-minute workouts three times a week for a year. Physical trainers monitor participants virtually via provided home exercise equipment or in person at the Arkansas Children’s Nutrition Center in Little Rock. 

Dr. Appell said early feasibility results — measured by recruitment, adherence and patient feedback on applicability — are encouraging. She plans to apply for an NIH K08 Mentored Clinical Scientist Development Award in early 2027, which would facilitate expanding the project to other sites. 

Dr. Appell noted anecdotally that, “Patients say they feel helpless and powerless when they get a diagnosis of ALL. They’ve commented that participating in this project empowers them to take charge of their health. It gives them hope of getting healthier while undergoing treatment.” 

Because the two projects target ALL patients, the principal investigators coordinated efforts by recruiting different age groups to ensure the studies did not unintentionally affect each other. 

 

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