A calorie-restricted diet combined with exercise for children and adolescents with acute lymphoblastic leukemia (ALL) was shown to reduce levels of detectable leukemia cells 1 month after the beginning of chemotherapy, according to a study published in Blood Advances.1
The Improving Diet and Exercise in ALL (IDEAL) trial (ClinicalTrials.gov Identifier: NCT02708108) sought to determine whether a modest 10% reduction in calorie intake during the induction phase of chemotherapy could reduce the levels of minimal residual disease (MRD) detected 1 month later. MRD at this stage is generally considered to be prognostic of survival and risk of relapse.
“Our work started around 15 years ago when the first reports came out showing that children who were obese when they were diagnosed with high-risk ALL had about a 50% higher relapse rate,” said Steven Mittelman, MD, PhD, chief of pediatric endocrinology at UCLA Mattel Children’s Hospital and a member of the UCLA Jonsson Comprehensive Cancer Center in Los Angeles, California.
Dr Mittelman developed mouse models in the laboratory to investigate the effect of obesity, showing that obese mice treated with leukemia chemotherapies had poorer outcomes, mimicking the clinical finding in obese children. Putting the mice on a calorie-restricted diet shortly before chemotherapy began improving outcomes,2 and a 2014 clinical study3 found that obese patients who became non-obese during therapy had a reduced risk of relapse.
“This concept of eating what the patients want, compounded by the lack of exercise, compounded by the chemotherapy, really creates this perfect storm of a problem where patients are just gaining fat almost unabated in this first month,” said Etan Orgel, MD, PhD, director of the medical supportive care service in the cancer and blood disease institute at Children’s Hospital in Los Angeles, California.
Following this preliminary work, the IDEAL trial was started to test whether a modest 10% reduction in calorific intake could reduce the impact of this fat gain on the levels of minimal residual disease (MRD) detected after 1 month of induction treatment. MRD level at this time is generally prognostic of outcomes including survival and relapse.
One of the significant findings was that the fat mass of all the patients in the study increased during the induction phase, but the intervention reduced this substantially, particularly in the overweight and obese patients.
“We saw that patients who were overweight in the first month had higher rates of minimal residual disease after induction therapy, an important predictor of survival for these patients,” said Dr Orgel.
In addition, the researchers found improved insulin sensitivity among the intervention group and increased levels of adiponectin, a hormone that is involved in regulating glucose and breaking down fatty acids. Overall, those in the intervention group had a 70% decrease in the chance of having detectable MRD at the end of induction therapy. As a control, a historical cohort was used, where differences in factors such as age, initial white blood cell count, cytogenetic risk category, sex, and ethnicity were taken into account for the comparisons.
The idea of caloric restriction for children and young adults who have just received a devastating diagnosis was not roundly met with enthusiasm from peers in the field initially, but the researchers reported excellent compliance with the calorie reduction intervention.
“The biggest obstacle we ran into when broaching this idea was people thinking, truly, that we were just crazy for trying this in the first month of treatment. How are we going to ask these patients to do more and more, when they’re already going through so much? We found the exact opposite. Families and patients were really looking for something that they could do to make their therapy work better,” Dr Orgel continued.