Children and adolescents with leukemia who were placed on a restrictive diet and exercise regimen concurrent with starting chemotherapy showed responses to treatment that were better than those historically seen in such patients.
This apparently improved response suggests it is possible to boost treatment efficacy without raising the dose – or toxicity – of chemotherapy.
“To our knowledge, this is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet and exercise to augment chemotherapy efficacy and improve disease response, the authors reported.
The findings come from the IDEAL pilot trial, conducted in 40 young patients (mean age, 15 years; range, 10-21 years) diagnosed with high-risk B-cell acute lymphoblastic leukemia (B-ALL).
The study was published online April 1 in Blood Advances.
The diet and exercise regimen is a departure from current recommendations for patients with leukemia.
“This was a major paradigm shift – until now, many oncologists encouraged ‘comfort foods’ and increased calories to get through the rigor of chemotherapy,” first author Etan Orgel, MD, of Children’s Hospital Los Angeles and the University of Southern California, also in Los Angeles.
The results from this pilot trial suggest that “the era of encouraging comfort food should be in the past; over-nutrition is likely harmful, and diet and exercise are important tools to harness during chemotherapy,” he said.
Dr. Orgel added that childhood ALL was selected because it is the most common cancer of childhood, but the findings could have potential relevance in other cancer types in children as well as adults.
Commenting on the study, Patrick Brown, MD, director of the pediatric leukemia program at Johns Hopkins University, Baltimore, said the findings are important, albeit preliminary.
“I think the most important contribution of this pilot study is to show that it is possible to change the nutrition and exercise habits of children and adolescents during the initial month of treatment for ALL,” he said in an interview.
“We have to be cautious about the preliminary finding that these changes resulted in deeper remissions – this will need to be confirmed in a larger study,” added Dr. Brown, who was not involved with the research.
Dr. Orgel noted that a prospective, randomized trial, IDEAL-2, is launching later this year to further evaluate the intervention.
Obesity linked to poorer chemotherapy response
Among children and adolescents who start treatment for B-ALL, as many as 40% are overweight or obese, noted the study authors.
Those who are obese have more than a twofold greater risk of having persistent minimal residual disease (MRD) at the end of chemotherapy, considered the strongest patient-level predictor of poor outcome and a common guide for therapy intensification.
The problem is compounded by weight gain that is common during treatment as a result of prolonged chemotherapy and sedentary behavior, they commented.
With studies of obese mice linking calorie and fat restriction to improved survival after chemotherapy, the authors theorized that a calorie- and fat-restrictive diet and exercise could help improve outcomes after chemotherapy in humans.
Participants were enrolled at Children’s Hospital Los Angeles and City of Hope National Medical Center in nearby Duarte. After they were started on chemotherapy, they were placed on a low-carb, low-fat, and low-sugar diet tailored to patient needs and preferences, as well as a moderate daily exercise regimen, and continued on this regimen throughout the 4-week induction phase.
Following the intervention, there were no significant reductions observed in median gain of fat mass at the end of the intervention, compared with baseline (P = .13). However, in the subgroup of patients who were overweight or obese at baseline, the reduction in fat mass was indeed significant versus baseline (+1.5% vs. +9.7% at baseline; P = .02).
Importantly, after adjustment for prognostic factors, adherence to the intervention was associated with a significant reduction in the risk of MRD, compared with recent historical controls who received the same induction therapy at the same institution, but no intervention (odds ratio, 0.30; P = .02).
The intervention was also associated with a lower detectable MRD, compared with the historical controls (OR, 0.16; one-sided P = .002).
“Most importantly, the IDEAL intervention reduced risk of MRD at the end of induction in all patients, irrespective of starting [body mass index] and after accounting for prognostic features,” the authors noted.