Peripheral Skeletal Muscle Impairment in Children After Treatment for Leukemia and Lymphoma

Exercise intolerance is a common adverse effect of childhood cancer, contributing to impaired health and well-being. While reduced aerobic fitness has been attributed to central cardiovascular deficiencies, the involvement of peripheral musculature has not been investigated. We studied peripheral muscle function in children following cancer treatment using noninvasive phosphorus-31 magnetic resonance spectroscopy. Ten acute lymphoblastic leukemia (ALL) and 1 lymphoma patient 8 to 18 years of age who completed treatment 6 to 36 months prior and 11 healthy controls participated in the study. Phosphorus-31 magnetic resonance spectroscopy was used to characterize muscle bioenergetics at rest and following an in-magnet knee-extension exercise. Exercise capacity was evaluated using a submaximal graded treadmill test. Both analysis of variance and Cohen d were used as statistical methods to determine the statistical significance and magnitude of differences, respectively, on these parameters between the patient and control groups. The patients treated for ALL and lymphoma exhibited lower anaerobic function (P=0.14, d=0.72), slower metabolic recovery (P=0.08, d=0.93), and lower mechanical muscle power (d=1.09) during exercise compared with healthy controls. Patients demonstrated lower estimated VO2peak (41.61 +/- 5.97 vs. 47.71 +/- 9.99 mL/min/kg, P=0.11, d=0.76), lower minutes of physical activity (58.3 +/- 35.3 vs. 114.8 +/- 79.3 min, P=0.12, d=0.99) and higher minutes of inactivity (107.3 +/- 74.0 vs. 43.5 +/- 48.3 min, d=1.04, P<0.05). Children treated for ALL and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise. Both deconditioning and direct effects of chemotherapy likely contribute to exercise intolerance in this population.

Automated summary

Exercise intolerance is a common adverse effect seen in children with cancer, and most studies have focused on the central cardiovascular deficiencies as the cause of reduced aerobic fitness. However, this study investigates the involvement of peripheral musculature using noninvasive phosphorus-31 magnetic resonance spectroscopy. The results show that children treated for acute lymphoblastic leukemia and lymphoma exhibit altered peripheral skeletal muscle metabolism during exercise, which could be attributed to both deconditioning and the direct effects of chemotherapy.