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. 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. 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. 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.
Other studies have been performed in the recent past, to understand how diet and exercise could enhamce the effectiveness of chemotherapy and improve the overall clinical outcome. The underlying biochemical mechanisms have still not been elucidated; yet, they could easily pinpointed in the cellular processes linked to some signaling pathways beneath fasting and cell autophagy. For example, fasting activates the AMPK protein kinase that trigger a program of metabolic adaptation and suppresses malignant cell proliferation. This very signaling is also stimulated by intense physical exercise and by drugs like metformin, an antidiabetic medication that has shown potential anticancer activities against secveral carcinomas, brain cancer and also blood malignancies. In this case, physical activity and calorie restriction would act sinergistically on this pathway.
Etan Orgel, MD, MS, Principal Investigator, Director, commented: “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”.
The study is published in the American Society of Hematology’s journal Blood Advances.
- Edited by Dr. Gianfrancesco Cormaci, PhD; specialist in Clinical Biochemistry.
Orgel E et al. Blood Advances 2021 Apr 13; 5(7):1853-1861.
Coombs A et al. Crit Rev Oncol Hematol. 2020; 152:103004.
Knips L et al. Cochrane Datab Syst Rev. 2019; 1(1):CD009075.
Simioni C et al. Oncotarget. 2018 Mar; 9(24):17199-17209.