Burden of sarcopenia and impact of structured physical programme in children with acute lymphoblastic leukaemia

Introduction

Background

In developed countries, the 5-year survival rate for children with cancer now exceeds 80%. Acute lymphoblastic leukaemia (ALL), the most common childhood malignancy, has a 5-year event-free survival (EFS) rate of approximately 90% in low-risk cases (1). In Hong Kong, the 5-year EFS rate for standard-risk childhood ALL is similarly close to 90% (2). As survival outcomes improve, attention has increasingly shifted toward treatment-related morbidities that may affect long-term health and quality of life.

Sarcopenia, defined by the presence of both low skeletal muscle mass and low muscle strength according to the Asian Working Group for Sarcopenia (AWGS) (3), has emerged as a clinically significant condition in oncology. In adult populations, sarcopenia has been reported in 43% to 79% of patients with esophagogastric cancer and 56% to 63% of those with pancreatic cancer (4). It has also been identified as a prognostic factor in lung cancer, breast cancer, and hematologic malignancies (5). Reduced muscular strength is associated with increased cardiovascular and all-cause mortality, as well as higher risk of hypertension and metabolic syndrome in both adults and children (6). Furthermore, a close interaction between bone and muscle metabolism has been proposed, suggesting that muscle loss may have broader musculoskeletal implications (7).

The pathophysiology of sarcopenia in paediatric ALL is likely multifactorial. Disease-related inflammation, aggressive chemotherapy, altered hormone concentrations, and nutritional compromise may all contribute (8). Muscle wasting can begin early during cancer treatment and may be progressive (9). Importantly, glucocorticoids—cornerstones of contemporary paediatric ALL treatment protocols—are administered in substantial cumulative doses. In the Chinese Children Cancer Group Acute Lymphoblastic Leukemia 2020 (CCCG-ALL 2020) protocol adopted locally, dexamethasone is incorporated during induction and subsequent treatment phases, resulting in prolonged steroid exposure (see Appendices 1,2). Glucocorticoids have been shown to induce muscle atrophy and wasting (10).

These effects occur during a critical period of growth and musculoskeletal development in children, potentially amplifying long-term consequences compared with adult populations. Despite these biological risks, studies evaluating sarcopenia in children and adolescents with cancer remain limited. Existing data are largely derived from Western cohorts, and differences in body composition between Asian and Western populations may limit generalizability. Moreover, regional data describing muscle mass deficits in Asian paediatric ALL populations are scarce.

Given this knowledge gap, we conducted a cross-sectional study to determine the prevalence of sarcopenia among children with ALL treated at Hong Kong Children’s Hospital following implementation of routine Dual-energy X-ray absorptiometry (DXA) surveillance. We hypothesized that a substantial proportion of children undergoing ALL therapy would demonstrate reduced muscle mass relative to age- and sex-specific reference values. In addition, we embedded a small pilot feasibility case series to explore the practicality of longitudinal muscle and functional assessment during structured exercise intervention.

Objective

The aim of this pilot study is to assess the prevalence of sarcopenia in patients being treated for ALL and to assess whether a pilot structured physical training intervention can improve the skeletal muscle mass and physical functioning of sarcopenic patients. We present this article in accordance with the STROBE reporting checklist (available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0003/rc).

Methods

Study design

This study comprised two components: (I) a cross-sectional analysis to determine the prevalence of low muscle mass in children with B-cell ALL (B-ALL) undergoing DXA assessment, and (II) an embedded pilot feasibility case series evaluating short-term longitudinal changes in a small subgroup participating in an exercise program. To estimate the prevalence of sarcopenia in the pediatric population with ALL, we reviewed the medical records of patients newly diagnosed with ALL between January 2022 and March 2024. There was a recently adopted in-house protocol since October 2022 with incorporation of DXA scan as part of the routine bone health surveillance. During the early implementation phase, adherence was incomplete; therefore, not all eligible patients underwent scanning. In this study, we specifically examined those who underwent DXA scans during their treatment. Measurements of muscle mass obtained from the DXA scans were collected for analysis.

For the interventional component, patients with newly diagnosed ALL were recruited to our study. They were tracked for changes in muscle mass and function during the treatment process based on the methodologies as elaborated below. Data were collected at time point 1 (T1), defined as within the first two months from disease diagnosis, and time point 2 (T2) which was defined as four to six months after the diagnosis. Participants received an 8-week physical training exercise program between the first and second time points.

Implementation of exercise training

The exercise program was formulated in collaboration with the Physiotherapy Department at Hong Kong Children’s Hospital. It consisted of two sessions per week, each lasting 60 minutes, and was supervised by physiotherapists. The following exercises were included: mini-press for lower limb strengthening and the Kinesis system aimed at strengthening various target muscle groups, such as the chest, back, and core muscles. In addition to equipment-based strengthening exercises, bodyweight exercises were utilized, using participants’ body weight as resistance to achieve strengthening goals.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Central Institutional Review Board of the Hospital Authority, Hong Kong SAR, China (IRB/REC Ref. No. PAED-2023-069), and all parents or legal guardians of patients provided informed consent.

Settings

Patients were recruited from the Haematology and Oncology Center of Hong Kong Children’s Hospital, Hong Kong.

Patient cohort

To estimate the prevalence of sarcopenia in the paediatric population with ALL, medical records of patients newly diagnosed with ALL between January 2022 and March 2024 were reviewed.

For the interventional component, eligible participants were children 6 to 17 years of age, newly diagnosed with ALL between April and June 2024. Patients were categorized into low risk, intermediate risk, and high-risk groups and treated according to the CCCG-ALL 2020 protocol. The entire treatment protocol entailed induction, consolidation, and continuation phases, which include re-induction, interim continuation, and maintenance. Agents used included dexamethasone, prednisone, vincristine, daunorubicin, PEG-asparaginase, cyclophosphamide, cytarabine, mercaptopurine, methotrexate, bortezomib, and triple intrathecal therapy (Appendix 1). Exclusion criteria included uncontrolled cardiac or pulmonary disease, uncontrolled seizures, disease relapse, prior bone marrow transplantation, terminal illness, hormone replacement therapy, need for sedation during DXA scanning, or any condition deemed unsuitable by the attending paediatric oncologist.

Variables

In our study, we defined sarcopenia as a Muscle Mass Index (MMI) being two standard deviations below the age- and sex-specific mean (z-score <−2). In the absence of universally accepted pediatric diagnostic criteria for sarcopenia, we operationally defined sarcopenia as an MMI z-score <−2 (i.e., two standard deviations below the age- and sex-specific mean), consistent with commonly used pediatric body composition thresholds for clinically significant deficit. MMI was calculated using the equation: whole body muscle mass/height² (kg/m²). The z-score is calculated to reflect how an individual’s result compares to age- and sex-specific reference values. We aligned our definition of sarcopenia with those adopted in previous studies, enabling comparison of our results with previously published data (11,12). A z-score <−2 was used to define sarcopenia to account for age- and sex-related variability in paediatric muscle development, as adult AWGS cut-offs are not applicable to growing children. In the absence of established z-score–based criteria for paediatric sarcopenia, we selected <−2 to represent a clinically meaningful and severe deviation from normative values. Whole-body MMI was selected as the primary DXA-derived muscle parameter for this exploratory pediatric analysis. Given the lack of standardized pediatric diagnostic criteria for sarcopenia and variability in muscle parameters used across studies, a single predefined measure (whole-body MMI) was used to ensure internal consistency.

Measurement

Measurement of muscle mass and muscle performance

Whole-body muscle mass was assessed using the Hologic Horizon A DXA system (304247M).

Muscle performance was assessed using handgrip strength, push-ups, one-minute sit-ups, sit-and-reach, and the six-minute and nine-minute run-walk tests.

Measurement of bone health

Bone mineral density (BMD) and trabecular bone score (TBS) were assessed using the DXA to explore the association between bone health and sarcopenia at the two aforementioned time points. BMD at the lumbar spine (L1–L4) and total body (less head) was measured.

Bias

Potential biases in this pilot study arise from voluntary participation and the absence of a control group, which were not specifically accounted for.

Study size

As this is a pilot study, calculation of sample size is not applicable.

Quantitative variables

The MMI obtained from the DXA scan in our study was compared to sex- and age-specific percentile reference values for MMI in Chinese children and adolescents aged 3 to 17 years. These reference values were derived from the China Child and Adolescent Cardiovascular Health (CCACH) Study, a large-scale, population-based cross-sectional study aimed at investigating skeletal muscle mass in children and adolescents aged 3 to 18 years living in urban areas of China (13).

The results of muscle performance in our study were then compared to established sex- and age-specific percentile reference values for physical fitness among Hong Kong Chinese children and adolescents aged 6 to 17 years, derived from a previous cross-sectional study utilizing data from the School Physical Fitness Award Scheme (SPFAS) (14). SPFAS is an electronic platform that collects anthropometric and fitness data from participating students, encompassing approximately half of all local schools in Hong Kong. This study measured various aspects of physical fitness, including handgrip strength, push-ups, one-minute sit-ups, sit-and-reach, and both six-minute and nine-minute run-walk tests, which were used to develop age- and sex-specific percentile reference values for skeletal muscle mass in this population (14).

For TBS, normative values for the paediatric population in Asia were limited, and we compared our data with paediatric reference values from American sources (15).

Confounder

One important confounder regarding sarcopenia was the baseline exercise level of the patients. To understand their baseline activity level, participants were asked to complete the Chinese University of Hong Kong Physical Activity Rating for Children and Youth (CUHK PARCY) Questionnaire, reflecting their self-rated overall weekly level of physical activity over the past twelve months (16). The CUHK-PARCY is an activity rating questionnaire that utilizes an 11-point scale [0–10] to assess levels of physical activity. This scale ranges from no exercise at all [0] to vigorous exercise on most days [10], considering the frequency, duration, and intensity of the activities involved. The results are expressed in metabolic equivalent (MET) units, where 1 MET represents the energy expenditure at rest, 3 METs indicate three times the resting energy expenditure, and so forth. Specifically, 3 METs correspond to a low level of physical activity, 5 METs refer to a moderate level, and 9 METs indicate a high level of physical activity (16) (Appendix 2).

Statistical analysis

Descriptive statistics were used to summarize the data. Continuous variables were reported as the median, accompanied by the interquartile range (IQR), while categorical variables were reported as frequencies. Tables and graphical representations were employed to visualize the data distribution. Inferential statistical methods were not applied, as the sample size was insufficient to draw generalized conclusions. All values, except for the TBS and the growth parameters z-score, were rounded to the nearest 0.1. The growth parameters z-score was rounded to the nearest 0.01, while the TBS was rounded to the nearest 0.001. In the research, Microsoft Excel was utilized as the primary tool for conducting statistical calculations.

Results

Prevalence of sarcopenia in patients with ALL

Participants

A total of 76 patients with newly diagnosed ALL were identified between January 2022 and March 2024. Their medical records were reviewed, revealing that 24 patients had at least one DXA scan performed during their treatment. The values from their initial DXA scans were analyzed.

Descriptive data

Among the 24 patients (mean age 10.8 years, IQR 8 to 14 years; 58.3% male) with newly diagnosed ALL were identified between January 2022 and March 2024 and at least one DXA scan performed during their treatment, 22 patients had B-ALL, which included 3 patients with Philadelphia chromosome-positive (Ph+) B-ALL and 5 with Ph-like B-ALL. Additionally, 2 patients had T-cell ALL. Of the patients who underwent DXA scans, 2 had their first scan during the induction phase, 3 during the consolidation phase, and 18 during the maintenance phase. One patient underwent hematopoietic stem cell transplantation (HSCT), and her DXA scan was conducted 1-year post-transplant. One patient was 18 years old.

Outcome data

One patient was 18 years old, and since there were no reference values for calculating z-scores for children older than 17 years, she was exempted from the prevalence calculation. For the remaining 23 patients with calculated MMI, the median MMI was 10.6 kg/m² (IQR 9.6 to 11.3 kg/m²). The median z-score for MMI was –1.1 (IQR –2.4 to –0.3). Six patients exhibited sarcopenia in their first DXA scan, with a median z-score for MMI of –2.5 (IQR –3.4 to –2.4).

Main results

For the 23 patients with calculated MMI, six patients exhibited sarcopenia in their first DXA scan. Therefore, the estimated prevalence of sarcopenia among paediatric patients with ALL was 26%.

Effects of structured physical training intervention on skeletal muscle mass and physical functioning

Participants

This pilot interventional study was conducted between April and June 2024. Twelve patients with newly diagnosed ALL were screened; four declined participations, one was excluded following revision of diagnosis to chronic myeloid leukaemia, and one was excluded due to disseminated candidiasis with hip abscess (Figure 1).

Figure 1 Participant flow diagram for the pilot structured exercise. IQR, interquartile range.

Six patients were ultimately enrolled and completed the 8-week structured exercise programme without dropouts. The median number of sessions attended was 15 (IQR 14–16), and no intervention-related adverse events were reported. This pilot intervention included a small cohort of six patients; therefore, results are presented descriptively.

Descriptive data

The median age of the participants was 8.5 years (IQR 7–9 years), and 4 (66.7%) were female. All patients had B-ALL, four patients were classified in the low-risk group, while two were in the intermediate-risk group. All patients were treated according to the CCCG-ALL-2020 protocol. The median baseline activity level, as self-reported using the CUHK PARCY Questionnaire, was 6 (IQR 5–6), indicating that the patients had a moderate level of physical activity at baseline. Their median body weight z-score was 0.27 (IQR 0.11–1.95), the median body height z-score was 0.18 (IQR −0.03 to 1.35), with the median BMI was 0.39 (IQR 0.15–0.80) at T1. At T2, their median body weight z-score was 0.55 (IQR −0.06 to 2.2), the mean body height z-score was 0.51 (IQR 0.05 to 1.35) and the median BMI z-score was 0.39 (IQR 0.19–0.67). All patients were found to have anaemia at presentation, with haemoglobin levels ranging from 4.9 to 8.5 g/dL. Four out of six patients reported symptoms of anaemia, including pallor and malaise, occurring from two weeks to three months prior to diagnosis, as indicated in the medical records.

The median time between diagnosis and T1 for patients undergoing DXA scans was 56 days (IQR 51–71 days). The median time between diagnosis and T1 for patients undergoing physical assessments was 55.5 days (IQR 48–66.5 days). The median time between diagnosis and T2 for patients undergoing DXA was 126.5 days (IQR 124.5–169 days); The median time between diagnosis and T2 for patients undergoing physical assessments was 206.5 days (IQR 188–217.5 days), reflecting differences in clinical scheduling and scan availability. At T1, two patients were in consolidation with high-dose methotrexate (HDMTX), three patients were spanning CAT and consolidation with HDMTX doses, and one patient was transitioning from induction to HDMTX. At T2, one patient was spanning consolidation to interim continuation week, two patients were in interim continuation week, one patient was spanning interim continuation week to reinduction, one patient was in reinduction, and one patient was spanning reinduction to maintenance.

The baseline characteristics of these patients, including cell counts at diagnosis, are presented in Table 1.

Outcome data

At T1, the median z-score for MMI was −1.5 (IQR −2.0 to −1.1). The median z-score for right handgrip was −0.5 (IQR −1.2 to 0.2). The median z-score for 6-minute run-walk was −2.6 (IQR −3.2 to −1.8). The median z-score for 9-minute run-walk was −3.0 (IQR −3.2 to −3.0). The median z-score for sit-and-reach was −1.5 (IQR −2.4 to −0.4). The median z-score for 1-minute sit-up was −2.5 (IQR −2.5 to −1.7). There were no age- and sex-specific reference values for push-ups in children under 12 years for calculation of z-score, median number of push-ups performed by patient was 0 repetitions (IQR 0–0). Patients had a median z-score for BMD (L1–L4) of −1.5 (IQR −2.1 to −1.2) and a median z-score for BMD (total body less head) of −1.6 (IQR −2.1 to −1.3). The median z-score for TBS was −0.1 (IQR −0.6 to 0.3) (Table 2, Figure 2).

Figure 2 Assessment of muscle mass and performance in patients at time points T1 and T2. BMD, bone mineral density; T1, time point 1; T2, time point 2; TBS, trabecular bone score.

At T2, the median z-score for MMI was −1.3 (IQR −1.7 to −0.8). The median z-score for right handgrip was −0.2 (IQR −0.8 to 0.1). The median z-score for 6-minute run-walk was −2.9 (IQR −3.0 to −0.3). The median z-score for 9-minute run-walk was −2.2 (IQR −2.3 to −2.1). The median z-score for sit-and-reach was −1.1 (IQR −1.2 to −0.5). The median z-score for 1-minute sit-up was −1.9 (IQR −2.2 to −1.6). There were no age- and sex-specific reference values for push-ups in children under 12 years for calculation of z-score, median number of push-ups performed by patient was 0 repetitions (IQR 0–0). Patients had a median z-score for BMD (L1–L4) of −2.6 (IQR −3.5 to −1.7) and a median z-score for BMD (total body less head) of −1.9 (IQR −2.3 to −1.6). The median z-score for TBS was 0.1 (IQR −0.6 to 0.5) (Table 2, Figure 2).

Main results

All six patients from the interventional cohort had low MMI and muscle performance values compared to age- and sex-specific reference values, with reference to the z-scores; two patients were diagnosed with sarcopenia at T1 and one of them continued to show signs of sarcopenia at T2.

At T1, all patients had low MMI and muscle performance values compared to age- and sex-specific reference values. All patients displayed low BMD compared to age- and sex-specific reference values. The TBS was relatively normal when compared to age- and sex-specific reference values.

At T2, four patients experienced an increase in their MMI. Four patients demonstrated an increase in their right handgrip from T1 to T2. All patients showed an increase in their 6/9-minute walk/run from T1 to T2. Five patients improved their sit-and-reach performance from T1 to T2. Three patients showed improvement in their 1-minute sit-up performance from T1 to T2. One patient showed improvement in his push-up performance from T1 to T2. Five patients’ BMD scores decreased from T1 to T2. Four patients showed an increase in their TBS from T1 to T2. Overall, despite ongoing leukaemia treatment, patients showed improvements in muscle mass and muscle performance from T1 to T2.

Discussion

To our understanding, this is the first study in Asia to comprehensively evaluate sarcopenia in pediatric patients with ALL. This study primarily reports cross-sectional prevalence data on low muscle mass in children with B-ALL, with an embedded pilot feasibility case series exploring longitudinal changes in a small exercise subgroup.

Key results

Based on our data from patients diagnosed with ALL between 2022 and 2024 who underwent DXA scans, we found that 26% exhibited sarcopenia, indicated by an MMI with z-score of less than −2. Our study also evaluated patients with newly diagnosed ALL and monitored changes in muscle mass and function throughout the treatment process. We reported on six patients with newly diagnosed ALL, all of whom displayed low muscle mass and strength in the early stages of the disease. Our study demonstrated that the assessment and implementation of an exercise program for children with cancer during early stage of therapy are feasible. In our study, we demonstrated that patients’ overall MMI and muscle performance improved following an 8-week structured physical training incorporated in an early stage of treatment course, despite the intense chemotherapy protocol. However, performance in the 1-minute sit-up and push-up assessments remained poor compared to other muscle evaluations. The correlation between BMD and sarcopenia was explored in our study. We noted an ongoing decline in BMD, despite improvements in muscle mass following exercise training.

Limitations

This study has several limitations that should be addressed. The small sample size, which includes only one cancer type, affects our estimation of sarcopenia prevalence. The indications and timing for patients undergoing DXA scans varied. Glucocorticoids are a crucial component of ALL treatment; however, only 32% (24 out of 76 patients) underwent DXA scans for screening purposes. Most DXA assessments were performed during maintenance therapy rather than at diagnosis. As a result, the reported 26% prevalence may not reflect sarcopenia at initial presentation. It is possible that prevalence at diagnosis could be higher, particularly given the effects of disease burden and early glucocorticoid exposure. Prospective assessment at standardized time points, including diagnosis and induction, is warranted.

Previous studies in survivors have indicated that sarcopenia is more prevalent among those with myeloid leukemia (17). It would be interesting to know if there are any differences in the prevalence of sarcopenia among pediatric patients with various cancer diagnoses. This intervention was conducted as a feasibility pilot study and was not designed as a randomized controlled trial. The small number of eligible patients during the recruitment period and clinical constraints during intensive chemotherapy limited the ability to implement randomization or include a matched control group. Consequently, causal inferences regarding the effects of the exercise programme cannot be established. Participation in the exercise intervention was voluntary, raising the possibility of selection bias. Formal comparisons between participants and non-participants were not conducted due to small sample size. It is possible that children with better baseline performance status, lower treatment-related symptom burden, or greater family support were more likely to enrol. Consequently, the observed improvements may not be generalizable to all patients undergoing similar chemotherapy protocols.

Future research should involve a larger cohort with a wider variety of cancer diagnoses to better understand the prevalence of sarcopenia in the paediatric cancer population. Including a control group would help mitigate this potential bias.

Interpretation

Research on sarcopenia in childhood cancer patients is relatively limited compared to studies focusing on adults. Most large-scale studies concentrate on cancer survivors, revealing varying prevalence rates of sarcopenia. For instance, a study involving over 2,000 Dutch childhood cancer survivors aged 18 to 45 years old found that 4.4% exhibited sarcopenia (18). In this study, sarcopenia was defined by low appendicular lean mass, indicated by a z-score of −1.5 or lower, and low muscle strength, measured by handgrip strength with a z-score of −1.5 or less. Survivors of myeloid leukemia were found to be more frequently affected. Another study of 116 pediatric cancer survivors with a median age of 12.1 years reported a sarcopenia prevalence of 37.9% (17). Sarcopenia in this study was diagnosed if the appendicular lean mass index z-score was −1.5 standard deviations or lower, along with handgrip strength below the 2nd centile.

In terms of assessing sarcopenia in patients currently undergoing treatment, the number of studies is fewer and generally smaller in scale, primarily focusing on ALL (10,19). One study involving 47 ALL patients with a median age of 8.6 years measured the psoas muscle area pre- and post-induction using computed tomography (CT) scans, calculating the muscle loss index (post-treatment psoas muscle area divided by pre-treatment psoas muscle area). They found that 30% of patients had sarcopenia, although this study focused solely on muscle mass without addressing functional aspects (19). Another study involving 105 ALL patients aged 3 to 18.8 years old in the maintenance phase aimed to evaluate the impact of dexamethasone on muscle mass and function. Sarcopenia was defined by low appendicular skeletal muscle mass (ASM) with a standardized deviation score (SDS) of −1.5 or lower and low handgrip strength with an SDS of −1.5 or lower. A total of 2.8% of patients were found to have sarcopenia (10). Additionally, one study explored sarcopenia in high-risk neuroblastoma patients by measuring changes in psoas muscle area, but it did not establish a cut-off for sarcopenia and did not assess muscle strength (20).

Based on our data from patients diagnosed with ALL between 2022 and 2024 who underwent DXA scans, we found that 26% exhibited sarcopenia, indicated by an MMI with z-score of less than −2. The variability in the prevalence of sarcopenia observed may be attributed to the different measurement methods employed in the studies and the varying criteria used for diagnosing sarcopenia. Although international consensus definitions in adults define sarcopenia as a syndrome comprising both low muscle mass and impaired muscle function, pediatric-specific criteria remain less well established. In this study, sarcopenia was defined based on low muscle mass using DXA-derived MMI z-scores. Functional performance measures were analyzed separately. Therefore, our prevalence estimate reflects a mass-based definition and should be interpreted within this methodological context. Although ASM is commonly used in adult sarcopenia definitions, pediatric-specific consensus criteria remain lacking. In this exploratory study, whole-body MMI was selected as the predefined muscle parameter. Future larger studies may consider incorporating multiple muscle indices to enhance comparability across populations.

As DXA was not uniformly performed in all newly diagnosed patients during the implementation phase, the reported 26% prevalence may be influenced by selection bias and should not be interpreted as population-representative. The CCACH Chinese reference dataset was selected because comprehensive, age- and sex-specific DXA-derived muscle mass reference values for Hong Kong children are currently limited. Given the shared ethnic background, these norms were considered the most appropriate available reference; however, regional differences in growth patterns cannot be excluded. It remains possible that the use of Hong Kong-specific paediatric reference values, if available, could alter the estimated prevalence of sarcopenia. Even small differences in normative means or standard deviations may influence classification when applying a z-score threshold of <−2. Future studies should consider validating or developing local reference standards to improve precision in prevalence estimation.

Our study also evaluated patients with newly diagnosed ALL and monitored changes in muscle mass and function throughout the treatment process. We reported on six patients with newly diagnosed ALL, all of whom displayed low muscle mass and strength in the early stages of the disease. Anaemia may contribute to these findings (21), as all patients were found to have anaemia at presentation, with haemoglobin levels ranging from 4.9 to 8.5 g/dL. It is plausible that reduced activity levels in paediatric cancer patients, caused by malaise secondary to anaemia, contributed to low muscle mass and diminished muscle performance.

All the patients received transfusions to maintain their haemoglobin levels at least at 7 g/dL during treatment. However, longitudinal haemoglobin levels and transfusion requirements were not systematically recorded during the intervention period, and correlations with functional improvement were not analysed. Improvements observed over eight weeks may therefore reflect, at least in part, haematologic recovery during therapy. Future studies should incorporate serial haemoglobin monitoring to better distinguish treatment-related recovery from exercise-induced adaptation. Furthermore, the induction chemotherapy may also play a significant role, as it typically involves a relatively intensive regimen aimed at eliminating leukemic cells; glucocorticoids, a cornerstone agent in the early treatment protocol for ALL, have been shown to induce muscle atrophy and wasting (10).

Despite the positive results of exercise interventions on fatigue and physical fitness in adults with cancer, evidence for similar benefits in children with cancer remains limited. A Cochrane review summarized the existing literature on the effectiveness of physical exercise training interventions in this population (22). Among the six studies reviewed, there was considerable heterogeneity in the mode and intensity of the exercise interventions. The number of children in each study was small, ranging from 13 to 51 participants. Notably, five out of the six studies implemented the exercise interventions during the maintenance treatment period. Our study demonstrated that the assessment and implementation of an exercise program for children with cancer during early stage of therapy are feasible. In our study, we demonstrated that patients’ overall MMI and muscle performance improved following an eight-week structured physical training incorporated in an early stage of treatment course, despite the intense chemotherapy protocol. However, performance in the 1-minute sit-up and push-up assessments remained poor compared to other muscle evaluations. This suggests that the endurance of abdominal and upper limb muscles may be less responsive to our exercise training program.

Improvements were more pronounced in aerobic performance measures (6- and 9-minute run-walk tests) than in upper-body endurance tests such as push-ups and sit-ups. This may reflect the relative emphasis of the intervention on aerobic and lower-limb activities, which were prioritized to enhance general conditioning and accommodate treatment-related fatigue. Upper-body resistance components were included but may not have provided sufficient stimulus to elicit measurable gains in muscular endurance. In a larger controlled trial, a more balanced or progressively intensified resistance component targeting both upper and lower body muscle groups may be warranted.

The median interval between T1 and T2 differed for physical performance testing (206 days) and DXA reassessment (126 days). During this period, participants were in later phases of therapy, spanning continuation to maintenance under the CCCG-ALL-2020 protocol. Although these phases are generally less intensive than induction or delayed intensification, variability in chemotherapy agents and cumulative exposure may occur both within and between phases. Therefore, treatment-related factors cannot be entirely excluded as contributors to the observed functional changes.

Previous studies on changes in BMD among pediatric cancer patients have shown a decline in BMD throughout the treatment course. For instance, a study by Inaba et al. examined BMD z-scores in 363 children with ALL and found that the median BMD z-score decreased from 0.06 at diagnosis to −1.08 by week 120 of treatment (23). The correlation between BMD and sarcopenia was explored in our study. The ongoing decline in BMD, despite improvements in muscle mass following exercise training, presents an interesting observation.

Despite improvements in physical performance, BMD continued to decline during the observation period. Cumulative glucocorticoid exposure and vitamin D status were not analysed in the present study. Given the well-established impact of glucocorticoids on bone metabolism and the high prevalence of vitamin D insufficiency in paediatric oncology populations, these factors may have contributed to the observed BMD reduction. In addition, the relatively modest intensity and duration of the exercise programme may not have been sufficient to mitigate treatment-related bone loss. Future studies should incorporate systematic assessment of cumulative steroid dose and vitamin D levels to better elucidate the interaction between chemotherapy, musculoskeletal adaptation, and exercise. Further investigation is required to better understand the interaction between glucocorticoid exposure, exercise dose, and bone adaptation in this population.

The CUHK-PARCY questionnaire captured baseline habitual activity prior to or at diagnosis. Following diagnosis and initiation of intensive chemotherapy, most patients experienced substantial reductions in habitual physical activity due to hospitalization and treatment-related fatigue, with structured physiotherapy sessions constituting the primary form of exercise during this period. Changes in habitual activity were not longitudinally quantified, nor was baseline activity level formally correlated with magnitude of improvement. Therefore, it remains unclear whether children with higher pre-diagnosis activity derived greater benefit from the structured intervention. Future studies should incorporate repeated activity assessments to better understand the relationship between habitual activity decline and responsiveness to exercise training.

Generalisability

A key strength of this study is its pioneering approach as the first prospective study to comprehensively evaluate sarcopenia in paediatric patients with ALL. It included a thorough assessment of muscle mass and various aspects of muscle function from the point of diagnosis, incorporating an exercise intervention early in the treatment protocol. This study involves a homogeneous and well-defined patient group, which enhances the clarity and reliability of the data. Although the sample size was limited, our findings indicated that a structured exercise intervention may help improve muscle performance and promote muscle mass growth, offering useful insights into managing sarcopenia in this patient group.

Conclusions

In conclusion, this pilot study suggests that structured physical training may improve muscle mass and endurance in paediatric patients with ALL, even during intensive chemotherapy. Routine assessment of muscle mass alongside bone density may help identify patients at risk of adverse musculoskeletal outcomes and facilitate timely referral to structured physical therapy programmes. Integrating tailored exercise interventions into standard treatment pathways could be beneficial for this vulnerable population. These findings underscore the importance of multidisciplinary collaboration among oncologists, endocrinologists, and physiotherapists to address the complex musculoskeletal needs of children with ALL. Given the feasibility demonstrated in this pilot, a multicentre parallel-group randomized controlled trial comparing structured early exercise with usual care would be warranted to establish efficacy. Assuming a moderate effect size, approximately 60 participants per group would likely be required to achieve adequate statistical power, with additional allowance for attrition.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0003/rc

Data Sharing Statement: Available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0003/dss

Peer Review File: Available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0003/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-2026-1-0003/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Central Institutional Review Board of the Hospital Authority Hong Kong SAR, China (IRB/REC Ref. No. PAED-2023-069), and informed consent was taken from all parents or legal guardians of patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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