Abstract: Apart from the five studies in the original review, this update included one additional RCT. In total, the analysis included 171 participants, all during treatment for childhood acute lymphoblastic leukaemia (ALL). The duration of the training sessions ranged from 15 to 60 minutes per session. Both the type of intervention and intervention period varied in all the included studies. However, the control group always received usual care. All studies had methodological limitations, such as small numbers of participants, unclear randomization methods, and single-blind study designs in case of one RCT and all results were of moderate to very low quality (GRADE). Cardiorespiratory fitness was evaluated by the 9-minute run-walk test, timed up-and-down stairs test, the timed up-and-go time test, and the 20-m shuttle run test. Data of the 9-minute run-walk test and the timed up-and-down stairs test could be pooled. The combined 9-minute run-walk test results showed significant differences between the intervention and the control groups, in favour of the intervention group (standardized mean difference (SMD) 0.69; 95% confidence interval (CI) 0.02 to 1.35). Pooled data from the timed up-and-down stairs test showed no significant differences in cardiorespiratory fitness (SMD -0.54; 95% CI -1.77 to 0.70). However, there was considerable heterogeneity (I2 = 84%) between the two studies on this outcome. The other two single-study outcomes, 20-m shuttle run test and the timed up-and-go test, also showed positive results for cardiorespiratory fitness in favour of the intervention group. Only one study assessed the effect of exercise on bone mineral density (total body), showing a statistically significant positive intervention effect (SMD 1.07; 95% CI 0.48 to 1.66). The pooled data on body mass index showed no statistically significant end-score difference between the intervention and control group (SMD 0.59; 95% CI -0.23 to 1.41). Three studies assessed flexibility. Two studies assessed ankle dorsiflexion. One study assessed active ankle dorsiflexion, while the other assessed passive ankle dorsiflexion. There were no statistically significant differences between the intervention and control group with the active ankle dorsiflexion test; however, in favour of the intervention group, they were found for passive ankle dorsiflexion (SMD 0.69; 95% CI 0.12 to 1.25). The third study assessed body flexibility using the sit-and-reach distance test, but identified no statistically significant difference between the intervention and control group. Three studies assessed muscle strength (knee, ankle, back and leg, and inspiratory muscle strength). Only the back and leg strength combination score showed statistically significant differences on the muscle strength end-score between the intervention and control group (SMD 1.41; 95% CI 0.71 to 2.11). Apart from one sub-scale of the cancer scale (Worries; P value = 0.03), none of the health-related quality of life scales showed a significant difference between both study groups on the end-score. For the other outcomes of fatigue, level of daily activity, and adverse events (all assessed in one study), there were no statistically significant differences between the intervention and control group. None of the included studies evaluated activity energy expenditure, time spent on exercise, anxiety and depression, or self efficacy as an outcome. The effects of physical exercise training interventions for childhood cancer participants are not yet convincing. Possible reasons are the small numbers of participants and insufficient study designs, but it can also be that this type of intervention is not as effective as in adult cancer patients. However, the first results show some positive effects on physical fitness in the intervention group compared to the control group. There were positive intervention effects for body composition, flexibility, cardiorespiratory fitness, muscle strength, and health-related quality of life (cancer-related items). These were measured by some assessment methods, but not all. However, the quality of the evidence was low and these positive effects were not found for the other assessed outcomes, such as fatigue, level of daily activity, and adverse events. There is a need for more studies with comparable aims and interventions, using a higher number of participants that also include diagnoses other than ALL.

Plain-language summary: We searched scientific databases for studies of comparing the effects of physical exercise training within the first five years following the diagnosis of childhood cancer compared with no training. Participants were under 19 years of age with any type of childhood cancer. The evidence is current to November 2014. This review included five randomized controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) and one clinical controlled trial (clinical studies where people are put into one of two or more treatment groups but this is not done in a random way) that evaluated the effects of a physical exercise training programme in children during cancer treatment. Childhood acute lymphoblastic leukaemia (ALL) is a cancer of the white blood cells and is the most common type of childhood cancer. For that reason, researchers often focus on this type of cancer since it will provide the largest number of patients in the shortest time-span. In total, our analysis included 171 participants with ALL. The results of the review showed that there were some small benefits of physical exercise training on body composition (percentage of fat mass, muscles, and bones), flexibility, cardiorespiratory fitness (how effective your heart and lungs are at delivering oxygen to your body), muscle strength and quality of life, but the evidence was limited. This can be related to an unsuitable programmes for children with cancer, or due to poorly designed studies. More studies assessing the effects of exercise are needed in a variety of childhood cancer populations. Furthermore, the current findings do not provide enough evidence to identify an optimal physical exercise training programme for children with cancer, neither do they provide information on the characteristics of people who will, or will not, benefit from such a programme. These important issues still need to be clarified.