Diet, exercise regimen improves efficacy of chemotherapy in youth with leukemia
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Caloric restriction through diet and exercise appeared to enhance the efficacy of chemotherapy among young patients with B-cell acute lymphoblastic leukemia, according to results of the IDEAL study published in Blood Advances.
The intervention reduced risk for minimal residual disease (MRD), which indicates improved response to treatment, results showed.
“During my career as a pediatric oncologist, I have seen chemotherapy for leukemia become increasingly intensive with more side effects but incrementally smaller benefits. The concept that nutrition and exercise can be used to make treatment both safer and more effective has been a well-founded theory for decades but had remained almost entirely unexplored in a clinical setting until now,” Etan Orgel, MD, MS, pediatric oncologist and director of medical supportive care services in the Children’s Center for Cancer and Blood Diseases at Children’s Hospital Los Angeles, told Healio.
Overweight and obesity are factors associated with chemotherapy resistance during induction for B-cell ALL. Orgel and colleagues hypothesized that an intervention consisting of caloric deficit and exercise would decrease fat gain during induction, reverse overweight physiology and, thus, improve B-cell ALL chemosensitivity, as indicated by reduction in MRD.
The analysis included 40 patients aged 10 to 21 years (mean age, 15 years ± 3; 60% male; 65% Hispanic) undergoing chemotherapy for high-risk B-cell ALL at Children’s Hospital Los Angeles and City of Hope National Medical Center from May 2016 to March 2019. Fifty percent of the population had obesity at baseline, and 15% were overweight.
Researchers compared this group with a recent historical control group of 80 patients (mean age, 14.7 years ± 2.5; 54% male; 83% Hispanic) treated between January 2008 and March 2014 for B-cell ALL using the same Children’s Oncology Group-induction regimen and eligibility criteria. Thirty-three percent of this group had obesity, and 11% were overweight.
The goal of the intervention — which began immediately after initiation of chemotherapy and prior to induction day 4 — was to induce a caloric deficit of at least 20%, divided equally between reduced calorie intake and increased exercise expenditure.
Patients recorded their dietary intake using 3-day food records and 24-hour recalls, and they attended weekly visits to reinforce the diet, along with optional phone calls.
The patients also received a personalized set of moderate to vigorous exercise options and wore Fitbit devices to measure home activity.
Percent change in fat mass during induction served as the study’s primary endpoint. Secondary endpoints included end-of-induction MRD — which was deemed positive using a threshold of at least 0.01%, and detectable as greater than 0% — as well as the feasibility of and adherence to the diet and exercise intervention.
Although the intervention did not significantly reduce fat mass from baseline overall compared with the control group (median change, +5.1% vs. +10.7%), analysis stratified by baseline BMI showed benefit among those with overweight and obesity (median change, +1.5% vs. +9.7%, P = .02).
After accounting for prognostic factors, the intervention significantly reduced risk for MRD positivity at end of induction (OR = 0.3, 95% CI, 0.09-0.92) and risk for detectable MRD (OR = 0.16; 95% CI, 0.04-0.52).
“Nutrition and exercise are crucial components of an ALL treatment plan,” Orgel said. “Not only may they reduce side effects, but even small changes to diet and calorie intake may dramatically improve the efficacy of chemotherapy. Of equal importance is that this intervention does not require a large cancer center or a lot of resources. It can be implemented in almost any treatment setting.”
Average adherence to diet was 82.1%, although researchers noted adherence to the exercise component was poor at 31.2%.
Researchers also acknowledged the use of a nonrandomized historical control for comparison as a limitation.
“Typically, we have allowed patients to eat what they want while going through such a difficult and overwhelming time,” Orgel said. “Yet, we saw patients coping with their diagnosis and with chemotherapy while also really embracing the changes to their diet. From our perspective, the patients felt empowered. Knowing they couldn’t control their disease or the chemotherapy, they were truly engaged in what they could control.”
The IDEAL-2 trial is underway to expand the cohort to include more patients from across the U.S.
“We anticipate that we will see similar improvements in the effectiveness of chemotherapy while also learning how to best implement this intervention in culturally diverse patient populations and settings,” Orgel said. “In the laboratory, my colleague and study co-investigator, Steven Mittelman, MD, PhD, will be studying the biological changes — how the intervention impacts leukemia cells — so that we can make the intervention even more effective for future patients.”
For more information:
Etan Orgel, MD, MS, can be reached at Children’s Hospital Los Angeles, Cancer and Blood Disease Institute, 4650 Sunset Blvd., MS#54, Los Angeles, CA 90027; email: eorgel@chla.usc.edu.
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