Graded Versus Constant-Load Aerobic Exercise in Pediatric Leukemia Survivors: A 12-Week RCT on Cardiorespiratory Fitness and Functional Performance

Background: Cardiorespiratory fitness is frequently impaired in survivors of pediatric acute lymphoblastic leukemia (ALL), limiting their functional performance. While aerobic exercise is recommended, evidence is needed to guide the prescription of specific training protocols in this population. Objective: This study sought to compare the efficacy of constant-load (CL-AEx) and graded aerobic exercise (G-AEx) protocols on cardiorespiratory fitness and functional capability in pediatric survivors of ALL. Methods: Seventy-two pediatric ALL survivors were allocated to CL-AEx, G-AEx, or a control group. Cardiopulmonary fitness [peak oxygen consumption (peak VO2), peak minute ventilation (VE), ventilatory equivalent for oxygen (VE/VO2), respiratory exchange ratio (RER), peak oxygen pulse (peak O2P), maximum heart rate (max HR), and one-minute heart rate recovery (HHR1)] and functional performance [six-minute walk test (6MWT), 4x10-m shuttle run test (4x10-mSRT), and timed up down stairs (TUDS)] were assessed at pre- and post-intervention. Results: The G-AEx group exhibited significantly enhanced cardiorespiratory and functional outcomes compared to both the CL-AEx and control groups (all p < 0.05). The G-AEx group demonstrated more pronounced improvements, showing significant increases in peak VO2, VE, VE/VO2, peak O2P, and HHR1, alongside a more efficient RER. Functionally, the G-AEx intervention led to superior improvements in 6MWT distance, and significantly faster completion times in the 4x10-mSRT and TUDS, highlighting multi-domain functional gain. Conclusions: In pediatric survivors of ALL, G-AEx demonstrated superior improvements in cardiorespiratory fitness and functional performance compared to CL-AEx over 12 weeks. These findings suggest that G-AEx is an effective modality for addressing acute physical deconditioning in this population. Incorporating G-AEx into clinical rehabilitation may enhance immediate physiological and functional recovery during the survivorship phase.