Substrate oxidation during exercise in childhood acute lymphoblastic leukemia survivors

Abstract

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%$\stackrel{\mathrm{̇}}{\mathrm{V}}$O₂peak) and was used to determine the MFO and the peak fat oxidation (Fat_max). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fat_max and crossover point were not different between the groups (p = .078; p = .765; p = .726). Fat_max and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) (p = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors’ substrate oxidation.

Keywords:

• Acute lymphoblastic leukemia
• cardiopulmonary exercise testing
• maximal fat oxidation
• pediatric cancer survivorship
• substrate oxidation

Disclosure statement

The authors report no conflicts of interest.

Data availability statement

Our data are not deposited in publicly available repositories. However, the datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Institute of Cancer Research (ICR) of the Canadian Institutes of Health Research (CIHR), in collaboration with C17 Council, Canadian Cancer Society (CCS), Cancer Research Society (CRS), Garron Family Cancer Centre at the Hospital for Sick Children, Ontario Institute for Cancer Research (OICR), and Pediatric Oncology Group of Ontario (POGO). This research was also supported in part by PhD study grants from Cole Foundation, Fonds de Recherche du Québec – Santé (FRQS), Sainte-Justine University Hospital Center Foundation and Foundation of Stars. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.