<p>Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common therapy for pediatric hematologic malignancies. With improved supportive care, addressing treatment-related late effects is at the forefront of survivor long-term health and quality of life. We previously demonstrated that alloHSCT survivors had increased adiposity, decreased lean mass, and lower bone density and strength, 7 years (median) from alloHSCT compared to their healthy peers. Yet it is unknown whether these deficits persist. Our longitudinal study characterized changes in muscle and bone over a period of 3.4 (range 2.0 to 4.9) years in 47 childhood alloHSCT survivors, age 5-26 years at baseline (34% female). Tibia cortical bone geometry and volumetric density and lower leg muscle cross-sectional area (MCSA) were assessed via peripheral quantitative computed tomography (pQCT). Anthropometric and pQCT measurements were converted to age, sex, and ancestry-specific standard deviation scores, adjusted for leg length. Muscle-specific force was assessed as strength relative to MCSA adjusted for leg length (strength Z-score). Measurements were compared to a healthy reference cohort (n=921), ages 5 to 30 years (52% female). At baseline and follow up, alloHSCT survivors demonstrated lower height-, weight-, and leg length Z-scores compared to the healthy reference cohort. Deficits in MCSA, trabecular volumetric bone density, and cortical bone size and estimated strength (section modulus) were evident in survivors (all p&lt;0.05). Between the two study time points, anthropometric, muscle, and bone Z-scores did not change significantly in alloHSCT survivors. Approximately 15% and 17% of alloHSCT survivors had MCSA and section modulus Z-score less than -2.0, respectively, at baseline and follow up. Furthermore, those with a history of total body irradiation compared to those without demonstrated lower MCSA at follow up. The persistent muscle and bone deficits in pediatric alloHSCT survivors support the need for strategies to improve bone and muscle health in this at-risk population. This article is protected by copyright. All rights reserved.</p>

<p><strong>BACKGROUND: </strong>Survival from paediatric high-risk neuroblastoma (HR-NBL) has increased, but cis-retinoic acid (cis-RA), the cornerstone of HR-NBL therapy, can cause osteoporosis and premature physeal closure and is a potential threat to skeletal structure in HR-NBL survivors. Sarcopenia is associated with increased morbidity in survivors of paediatric malignancies. Low muscle mass may be associated with poor prognosis in HR-NBL patients but has not been studied in these survivors. The study objective was to assess bone density, body composition and muscle strength in HR-NBL survivors compared with controls.</p>

<p><strong>METHODS: </strong>This prospective cross-sectional study assessed areal bone mineral density (aBMD) of the whole body, lumbar spine, total hip, femoral neck, distal 1/3 and ultradistal radius and body composition (muscle and fat mass) using dual-energy X-ray absorptiometry (DXA) and lower leg muscle strength using a dynamometer. Measures expressed as sex-specific standard deviation scores (Z-scores) included aBMD (adjusted for height Z-score), bone mineral apparent density (BMAD), leg lean mass (adjusted for leg length), whole-body fat mass index (FMI) and ankle dorsiflexion peak torque adjusted for leg length (strength-Z). Muscle-specific force was assessed as strength relative to leg lean mass. Outcomes were compared between HR-NBL survivors and controls using Student's t-test or Mann-Whitney U test. Linear regression models examined correlations between DXA and dynamometer outcomes.</p>

<p><strong>RESULTS: </strong>We enrolled 20 survivors of HR-NBL treated with cis-RA [13 male; mean age: 12.4&nbsp;±&nbsp;1.6&nbsp;years; median (range) age at therapy initiation: 2.6 (0.3-9.1) years] and 20 age-, sex- and race-matched controls. Height-Z was significantly lower in HR-NBL survivors compared with controls (-1.73&nbsp;±&nbsp;1.38 vs. 0.34&nbsp;±&nbsp;1.12, P&nbsp;&lt;&nbsp;0.001). Areal BMD-Z, BMAD-Z, FMI-Z, visceral adipose tissue and subcutaneous adipose tissue were not significantly different in HR-NBL survivors compared with controls. Compared with controls, HR-NBL survivors had lower leg lean mass-Z (-1.46&nbsp;±&nbsp;1.35 vs. -&nbsp;0.17&nbsp;±&nbsp;0.84, P&nbsp;&lt;&nbsp;0.001) and strength-Z (-1.13&nbsp;±&nbsp;0.86 vs. -&nbsp;0.15&nbsp;±&nbsp;0.71, P&nbsp;&lt;&nbsp;0.001). Muscle-specific force was lower in HR-NBL survivors compared with controls (P&nbsp;&lt;&nbsp;0.05).</p>

<p><strong>CONCLUSIONS: </strong>Bone mineral density and adiposity are not severely impacted in HR-NBL survivors with growth failure, but significant sarcopenia persists years after treatment. Future studies are needed to determine if sarcopenia improves with muscle-specific interventions in this population of cancer survivors.</p>

<p><strong>BACKGROUND: </strong>The survival of patients with high-risk neuroblastoma has increased with multimodal therapy, but most survivors demonstrate growth failure.</p>

<p><strong>OBJECTIVE: </strong>To assess physeal abnormalities in children with high-risk neuroblastoma in comparison to normal controls by using diffusion tensor imaging (DTI) of the distal femoral physis and adjacent metaphysis.</p>

<p><strong>MATERIALS AND METHODS: </strong>We prospectively obtained physeal DTI at 3.0&nbsp;T in 20 subjects (mean age: 12.4&nbsp;years, 7 females) with high-risk neuroblastoma treated with high-dose cis-retinoic acid, and 20 age- and gender-matched controls. We compared fractional anisotropy (FA), normalized tract volume (cm/cm) and tract concentration (tracts/cm) between the groups, in relation to height Z-score and response to growth hormone therapy. Tractography images were evaluated qualitatively.</p>

<p><strong>RESULTS: </strong>DTI parameters were significantly lower in high-risk neuroblastoma survivors compared to controls (P&lt;0.01), particularly if the patients were exposed to both cis-retinoic acid and total body irradiation (P&lt;0.05). For survivors and controls, DTI values were respectively [mean ± standard deviation]: tract concentration (tracts/cm), 23.2±14.7 and 36.7±10.5; normalized tract volume (cm/cm), 0.44±0.27 and 0.70±0.21, and FA, 0.22±0.05 and 0.26±0.02. High-risk neuroblastoma survivors responding to growth hormone compared to non-responders had higher FA (0.25±0.04 and 0.18±0.03, respectively, P=0.02), and tract concentration (tracts/cm) (31.4±13.7 and 14.8±7.9, respectively, P&lt;0.05). FA, normalized tract volume and tract concentration were linearly related to height Z-score (R&gt;0.31; P&lt;0.001). Qualitatively, tracts were nearly absent in all non-responders to growth hormone and abundant in all responders (P=0.02).</p>

<p><strong>CONCLUSION: </strong>DTI shows physeal abnormalities that correlate with short stature in high-risk neuroblastoma survivors and demonstrates response to growth hormone treatment.</p>