Overweight children and adolescents receiving chemotherapy for treatment of leukemia are less successful battling the disease compared to their lean peers. Now, research conducted at the Cancer and Blood Disease Institute at Children's Hospital Los Angeles indicates that modest changes in diet and exercise can greatly increase survival in youth treated for acute lymphoblastic leukemia (ALL), the most common childhood cancer.
To our knowledge, this is the first study to show that by limiting calories and increasing exercise we can make chemotherapy more effective in eliminating leukemia cells within the first month of therapy, decreasing the chances of disease relapse in children and adolescents."
Etan Orgel, MD, MS, Principal Investigator, Director of the Medical Supportive Care Service in the Cancer and Blood Disease Institute, Children's Hospital Los Angeles
The study is published in the American Society of Hematology's journal Blood Advances.
Youth who are obese when they begin chemotherapy are more than twice as likely to have remaining cancer cells after one month of treatment--and an increased chance of disease relapse--compared to their lean counterparts. To address this, the investigators worked with registered dietitians and physical therapists who created personalized diet and exercise plans for 40 patients between the ages of 10 and 21 with newly diagnosed leukemia.
The investigators found that patients who reduced their caloric intake by at least 10% and began a modest exercise regimen beginning at diagnosis were, on average, 70% less likely to have remaining leukemia cells in their bone marrow one month after beginning chemotherapy, compared to previously treated patients who did not participate in the diet and exercise intervention. Remaining leukemia cells, called minimal residual disease, is one of the strongest predictors of poor survival outcomes.
"This is proof of concept that it is possible to increase the effectiveness of chemotherapy without adding other medications and their potential side effects," says Dr. Orgel, who is also an associate professor of clinical pediatrics at the Keck School of Medicine of USC. "This short-term intervention is inexpensive and easily available to providers and families everywhere."
The investigators found that by limiting fat, patients also had decreased insulin resistance as well as increased levels of adiponectin, a metabolic hormone associated with glucose regulation. Identification of these potential biomarkers paves the way to using this intervention to impact other types of cancer.
"Changing diet and exercise made the chemotherapy work better-- that's the big news of this study. But we also need to figure out how," says Steven Mittelman, MD, PhD, Chief of Pediatric Endocrinology at UCLA Mattel Children's Hospital and member of UCLA's Jonsson Comprehensive Cancer Center. "Understanding the biological changes responsible for this effect will help us make these interventions even better." Dr. Mittelman co-led the study and was senior author on the paper.
This clinical trial, called Improving Diet and Exercise in ALL (IDEAL-1), builds on basic and preclinical research conducted for more than a decade at Children's Hospital Los Angeles. This "bench-to-bedside and back" approach provides new insights for treating devastating diseases, like cancer. Physicians observe an unmet clinical need in their patients, collaborate with colleagues in the lab and can then deliver an intervention to the clinic to test its effectiveness.
A randomized trial is planned for later this year. Called IDEAL-2, the study will be conducted by Dr. Orgel and Dr. Mittelman through the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) consortium, headquartered at Children's Hospital Los Angeles under the medical leadership of Alan Wayne, MD, and Deepa Bhojwani, MD.
Orgel, E., et al. (2021) Caloric and nutrient restriction to augment chemotherapy efficacy for acute lymphoblastic leukemia: the IDEAL trial. Blood Advances. doi.org/10.1182/bloodadvances.2020004018.