Dexamethasone-Induced Sarcopenia and Physical Frailty in Children With Acute Lymphoblastic Leukemia: Protocol for a Prospective Cohort Study

Verwaaijen, Emma J.; Hulst, Annelienke M. van; Fiocco, Marta; Hartman, Annelies; Grootenhuis, Martha; Pluijm, Saskia M. F.; Pieters, Rob; Akker, Erica van den; Heuvel‐Eibrink, Marry van den

doi:10.2196/33517

Cited by 5 publications

(12 citation statements)

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“…According to the European Working Group on Sarcopenia in Older People (EWGSOP), frailty is a multidimensional syndrome that increases vulnerability to poor health outcomes. It has been historically labeled as a "geriatric" condition as it is strictly related to aging, even if recent studies have begun to translate this concept in pediatric patients with chronic diseases (3,(33)(34)(35). Frailty encompasses both social and physical domains, with sarcopenia representing the main determinant.…”

Section: Discussionmentioning

confidence: 99%

Sarcopenia in children with chronic liver disease: Prevalence and impact on liver transplant outcomes

Veraldi

Pietrobattista²,

Soglia³

et al. 2022

Front. Pediatr.

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Sarcopenia is a clinical condition characterized by a reduction in muscle mass, which typically affects adult patients; however, it has recently been recognized in pediatric literature. Few studies in children with chronic liver disease (CLD) undergoing liver transplantation (LT) have investigated the role of sarcopenia, with controversial results. The aim of our study was to assess the prevalence and impact of sarcopenia among children with CLD who are candidates for LT. We conducted a retrospective, single-center study at Bambino Gesù Children's Hospital (Rome, Italy) from July 2016 to July 2021, evaluating all children (0–16 years old) with CLD listed for LT with an abdomen computed tomography imaging available before LT. The total psoas muscle surface area (t-PMSA) was defined as the sum of left and right psoas muscle surface area measured at L4–L5 on axial images. The t-PMSA z-score was calculated according to reference data, and sarcopenia was defined as a t-PMSA z-score of ≤−2 (1–16 years) or a psoas muscle index [PMI; PMI = t-PMSA/(100 × BSA)] of <50th percentile of the population examined (<1 year). Clinical, laboratory, and LT outcome data were collected from all the patients with CLD. 27 out 48 (56%) of the patients aged 1–16 years were sarcopenic. No differences were noted in anthropometrics, nutritional support, liver function tests, model for ESLD (MELD), or pediatric ESLD (PELD) scores between patients with and without sarcopenia. The former showed a higher prevalence of respiratory complications (66.7% vs. 42.1%) and need for inotropes (40.7% vs. 10.8%) after LT. Among patients aged 0–1 years (n: 36), those with reduced muscle mass (50%) had a longer hospitalization time (44 vs. 24 days) and higher incidences of multi-organ failure syndrome (38.9% vs. 0%) and intensive care unit-related infections (61.1% vs. 27.8%) compared to those with greater muscle mass. t-PMSA and PMI were statistically significant predictors of LT outcomes. Sarcopenia is a reliable index of frailty in children with CLD, as its presence is associated with the risk of a more challenging LT. Future studies will have to investigate the functional aspects of sarcopenia and conceive preventive measures of muscle wasting in CLD patients.

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Section: Discussionmentioning

confidence: 99%

Sarcopenia in children with chronic liver disease: Prevalence and impact on liver transplant outcomes

Veraldi

Pietrobattista²,

Soglia³

et al. 2022

Front. Pediatr.

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“…This study on sarcopenia and physical frailty was performed within the framework of the DexaDays‐2 study: a national randomized controlled trial on neurobehavioral side effects of dexamethasone in pediatric ALL patients aged 3–18 years, conducted at the Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands, between 2019 and 2021. The design of this study including in‐ and exclusion criteria has been previously described 23,24 …”

Section: Methodsmentioning

confidence: 99%

“…The design of this study including in-and exclusion criteria has been previously described. 23,24 From 2011 tot 2020, children with ALL were treated according to the Dutch Childhood Oncology ALL-11 protocol. In this protocol, patients were stratified to standard, medium, or high risk treatment.…”

Section: Study Design and Cohortmentioning

confidence: 99%

“…25 All participating patients had a sarcopenia/frailty assessment in the outpatient clinic, on the first day of a 5-day dexamethasone course (T1) and on the day after this same course (T2). The assessment consisted of measurements of fatigue, muscle mass, muscle strength, and physical performance, 24 and Conclusion: Physical frailty increased strikingly after a 5-days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.…”

Section: Study Design and Cohortmentioning

confidence: 99%

“…A complete overview of the measuring instruments including methods and psychometric properties have previously been described in our study protocol. 24 2.2.6 | Definition of sarcopenia and physical frailty Sarcopenia was defined as the combination of low muscle strength and low muscle mass. 3 Prefrailty and frailty were classified as the presence of respectively two, or more than two of the following five components: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity.…”

Section: Physical Activitymentioning

confidence: 99%

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Physical frailty deteriorates after a 5‐day dexamethasone course in children with acute lymphoblastic leukemia, results of a national prospective study

Verwaaijen,

van Hulst,

Hartman

et al. 2023

Cancer Medicine

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BackgroundDexamethasone is important in the treatment for pediatric acute lymphoblastic leukemia (ALL) but induces muscle atrophy with negative consequences for muscle mass, muscle strength, and functional abilities. The aim of this study was to establish the effect of a dexamethasone course on sarcopenia and physical frailty in children with ALL, and to explore prognostic factors.MethodsPatients with ALL aged 3–18 years were included during maintenance therapy. Patients had a sarcopenia/frailty assessment on the first day of (T1) and on the day after (T2) a 5‐day dexamethasone course. Sarcopenia was defined as low muscle strength in combination with low muscle mass. Prefrailty and frailty were defined as having two or ≥three of the following components, respectively: low muscle mass, low muscle strength, fatigue, slow walking speed, and low physical activity. Chi‐squared and paired t‐tests were used to assess differences between T1 and T2. Logistic regression models were estimated to explore patient‐ and therapy‐related prognostic factors for frailty on T2.ResultsWe included 105 patients, 61% were boys. Median age was 5.3 years (range: 3–18.8). At T1, sarcopenia, prefrailty, and frailty were observed in respectively 2.8%, 23.5%, and 4.2% of patients. At T2, the amount of patients with frailty had increased to 17.7% (p = 0.002), whereas the number of patients with sarcopenia and prefrailty remained similar. Higher ASMM (odds ratio [OR]: 0.49, 95% CI: 0.28–0.83), stronger handgrip strength (OR: 0.41, 95% CI: 0.22–0.77) and more physical activity minutes per day (OR: 0.98, 95% CI: 0.96–0.99) decreased the risk of frailty at T2. Slower walking performance (OR: 2, 95% CI: 1.2–3.39) increased the risk. Fatigue levels at T1 were not associated with frailty at T2.ConclusionPhysical frailty increased strikingly after a 5‐days dexamethasone course in children with ALL. Children with poor physical state at start of the dexamethasone course were more likely to be frail after the course.

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The utility of a portable muscle ultrasound in the assessment of muscle alterations in children with acute lymphoblastic leukaemia

Verwaaijen

Hulst

Molinger

et al. 2023

J cachexia sarcopenia muscle

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BackgroundDuring treatment for acute lymphoblastic leukaemia (ALL), children are prone to musculoskeletal deterioration. However, non‐invasive tools to measure muscle mass and intramuscular alterations are limited. In this study we explored the feasibility of muscle ultrasound in children with ALL. Additionally, we analysed whether automated ultrasound outcomes of muscle size and intramuscular fat infiltration (IMAT) were associated with appendicular skeletal muscle mass (ASMM), muscle strength and physical performance.MethodsChildren with ALL, aged 3–18 years were included during maintenance therapy. Bilateral images of the rectus femoris muscle were captured using a portable linear array transducer connected to a tablet. Subsequently, an automated image annotation software (MuscleSound) was used to estimate cross‐sectional area, muscle thickness and IMAT. Feasibility was assessed using acceptance (percentage of children approached who were enrolled), practicality (percentage of children that completed the ultrasound measurement after enrolment) and implementation (percentage of children that had sufficient imaging to be processed and analysed by the software). Assessments of ASMM by bioimpedance analysis, muscle strength using handheld dynamometry and timed physical performance tests were administered at the same visit. Multivariable linear models were estimated to study the associations between muscle ultrasound outcomes and ASMM, strength and physical performance, adjusted for sex, age, body mass index and ALL treatment week.ResultsMuscle ultrasound was performed in 60 out of 73 invited patients (76.9%), of which 37 were boys (61.7%), and median age was 6.1 years (range: 3–18.8 years). The acceptance was 98.7%, practicality 77.9% and implementation was 100%. Patients who refused the examination (n = 13) were younger (median: 3.6, range: 3–11.2 years) compared with the 60 examined children (P = 0.0009). In multivariable models, cross‐sectional area was associated with ASMM (β = 0.49 Z‐score, 95% confidence interval [CI]:0.3,2.4), knee‐extension strength (β = 16.9 Newton [N], 95% CI: 4.8, 28.9), walking performance (β = −0.46 s, 95% CI: −0.75, −0.18) and rising from the floor (β = −1.07 s, 95% CI: −1.71, −0.42). Muscle thickness was associated with ASMM (β = 0.14 Z‐score, 95% CI: 0.04, 0.24), knee‐extension strength (β = 4.73 N, 95% CI: 0.99, 8.47), walking performance (β = −0.13 s, 95% CI: −0.22, −0.04) and rising from the floor (β = −0.28 s, 95% CI: −0.48, −0.08). IMAT was associated with knee‐extension strength (β = −6.84 N, 95% CI: −12.26, −1.41), walking performance (β = 0.2 s, 95% CI: 0.08, 0.32) and rising from the floor (β = 0.54 s, 95% CI: 0.27, 0.8). None of the muscle ultrasound outcomes was associated with handgrip strength.ConclusionsPortable muscle ultrasound appears a feasible and useful tool to measure muscle size and intramuscular alterations in children with ALL. Validation studies using magnetic resonance imaging (gold standard) are necessary to confirm accuracy in paediatric populations.

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Dexamethasone-Induced Sarcopenia and Physical Frailty in Children With Acute Lymphoblastic Leukemia: Protocol for a Prospective Cohort Study

Cited by 5 publications

References 71 publications

Sarcopenia in children with chronic liver disease: Prevalence and impact on liver transplant outcomes

Sarcopenia in children with chronic liver disease: Prevalence and impact on liver transplant outcomes

Physical frailty deteriorates after a 5‐day dexamethasone course in children with acute lymphoblastic leukemia, results of a national prospective study

The utility of a portable muscle ultrasound in the assessment of muscle alterations in children with acute lymphoblastic leukaemia

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