Acute lymphoblastic leukemia (ALL) is the most common blood cancer of children and adolescents. Remarkable progress has been made in treating this deadly disease, but many children suffer relapses despite these advances. There are mounting data showing that lifestyle factors, specifically levels of exercise and nutritional intake, can have measurable and substantial impact on how well patients with a variety of cancers respond to treatment. It is not surprising that children and adolescents who have survived ALL tend to exercise less and be less fit than otherwise healthy subjects. But very little is known in pediatric patients with ALL about how exercise might be beneficial and prolong disease-free intervals. Recently, the National Cancer Institute (NCI) put out a call for research proposals designed to test mechanisms through which lifestyle interventions like exercise might prolong survivorship in cancer patients. The NCI specifically stressed the need to better understand the biological mechanisms through which behaviors like exercise could benefit cancer patients.

Exciting work in our laboratory (HS# 2002-2598) demonstrates the substantial effect that exercise has on white blood cell gene expression. Our data actually suggest heretofore undiscovered mechanisms that might explain why exercise might be beneficial for children and teenagers treated with ALL.

Under under HS#2012-9248, 8 pediatric ALL patients and 7 healthy controls, will be tested (for an overall sample size of 15) with, cardiopulmonary exercise testing used routinely to measure fitness in children. These data will provide us with essential information about fitness, and the immune system response to exercise in these patients and will be used to develop a broader set of studies and exercise interventions that, hopefully, will identify the ways in which exercise can serve as an adjunct to standard therapy for children with ALL.

Acute lymphocytic leukemia (ALL) is the most common hematological malignancy in children and adolescents. The gratifying and dramatic improvement in the survivorship of ALL is a testament to the strength of collaborative, multidisciplinary translational research efforts. Yet many gaps in our fundamental knowledge of disease mechanisms in ALL remain and hamper our ability to prolong remission and decrease disease relapse. There is increasing evidence that environmental, lifestyle factors such as physical exercise and fitness may play a beneficial role in cancer survivorship. The NCI has recently posted a Program Announcement to stimulate research on the impact of lifestyle interventions (e.g., exercise, nutrition) on cancer survivorship. The goal of this project is a development of a series of novel, hypothesis-driven proof of concept studies to explore ways in which exercise might benefit survivorship in ALL. The purpose of this initial project and Institutional Review Board (IRB) application is to gather minimally invasive data about patterns of physical activity and exercise, and leukocyte genomic response to exercise in children treated for ALL. These data will be essential in developing a larger protocol in response to the National Cancer Institute Program Announcement (NCI PA), one that addresses the NCI challenge that, "The biobehavioral mechanisms and pathways through which lifestyle interventions may increase survival following cancer are unknown." In addition, a number of studies have demonstrated that cardiovascular risk factors (such as BMI) in ALL survivors deteriorate following therapy. Exercise training interventions can improve cardiovascular risk in these patients; however, are difficult to implement in this population.

Consequently, in preparation for a larger study of exercise training on leukocyte genomic and epigenetic responses in ALL survivors, an essential biobehavioral component of any training study will be tested, namely, readiness for exercise training using approaches developed by researchers in our group. This part of our research will help us identify and target the unique set of fears and obstacles that almost invariably accompany children and adolescents (and their caregivers) who survive life-threatening diseases.

Inclusion Criteria:

• Ages 10-17 (males and females)
• Diagnosed with ALL in remission stage
• No evidence of disability that would impair participation in a vigorous physical activity challenge

Exclusion Criteria:

• Pregnancy or breastfeeding
• Use of illegal drugs or alcohol
• Other conditions that preclude exercise (such as neuromotor disease, heart disease, or any other condition that would prevent a child from participating in vigorous physical activity)