Patients with acute lymphoblastic leukemia (ALL) undergoing induction decrease their physical capacity, lose muscle mass, and decrease their quality of life (QOL). The safety, feasibility, and benefits of exercise during chemotherapy have been proven, but the effects of cross-training activities have yet to be analyzed. To measure the effects of cross-training on body composition, physical performance, and QOL, a blind randomized clinical trial was carried out. A total of 33 patients were included and randomized into a cross-training exercise group (CEG), a resistance exercise group (REG), and a control group (CG). During induction, patients received an exercise routine three to five days a week for 30 to 50 min each. Body composition, QOL, and physical performance were measured at baseline, up to discharge, and at a follow-up of two months. Body composition improved in the REG and CEG. In the CG, muscle mass decreased and fat mass increased (p = 0.020 and 0.020, respectively). The REG and CEG had significant positive improvements in physical performance compared to the CG. QOL showed no differences in any group (p = 0.340). Cross-training and resistance exercise are essential to improve body composition and physical performance during induction. Considering the prognostic value of physical performance, we propose integrated training exercises as adjuvant therapy in adult patients with ALL.

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