Skeletal, neuromuscular and fitness impairments among children with newly diagnosed acute lymphoblastic leukemia

Kirsten K Ness, Sue C Kaste, Liang Zhu, Ching-Hon Pui, Sima Jeha, Paul C Nathan, Hiroto Inaba, Karen Wasilewski-Masker, Durga Shah, Robert J Wells, Robyn E Karlage, Leslie L Robison, Cheryl L Cox, Kirsten K Ness, Sue C Kaste, Liang Zhu, Ching-Hon Pui, Sima Jeha, Paul C Nathan, Hiroto Inaba, Karen Wasilewski-Masker, Durga Shah, Robert J Wells, Robyn E Karlage, Leslie L Robison, Cheryl L Cox

Abstract

This study describes skeletal, neuromuscular and fitness impairments among 109 children (median age 10 [range 4-18] years, 65.1% male, 63.3% white) with acute lymphoblastic leukemia (ALL). Outcomes were measured 7-10 days after diagnosis and compared to age- and sex-specific expected values. Associations between function and health-related quality of life (HRQL) were evaluated with logistic regression. Children with ALL had sub-optimal bone mineral density (BMD) Z-score/height (mean ± standard error: - 0.53 ± 0.16 vs. 0.00 ± 0.14, p < 0.01), body mass index percentile (57.6 ± 3.15 vs. 50.0 ± 3.27%, p = 0.02), quadriceps strength (201.9 ± 8.3 vs. 236.1 ± 5.4 N, p < 0.01), 6 min walk distance (385.0 ± 13.1 vs. 628.2 ± 7.1 m, p < 0.001) and Bruininks-Oseretsky Test of Motor Proficiency scores (23 ± 2.5 vs. 50 ± 3.4%, p < 0.01). Quadriceps weakness was associated with a 20.9-fold (95% confidence interval 2.5-173.3) increase in poor physical HRQL. Children with newly diagnosed ALL have weakness and poor endurance and may benefit from early rehabilitation that includes strengthening and aerobic conditioning.

Trial registration: ClinicalTrials.gov NCT00902213.

Keywords: Acute lymphoblastic leukemia; muscle strength; pediatric; physical endurance; quality of life.

Figures

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Figure 1
Consort diagram

References

    1. Kaste SC, Rai SN, Fleming K, et al. Changes in bone mineral density in survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2006;46:77–87.
    1. Le Meignen M, Auquier P, Barlogis V, et al. Bone mineral density in adult survivors of childhood acute leukemia: impact of hematopoietic stem cell transplantation and other treatment modalities. Blood. 2011;118:1481–1489.
    1. Makitie O, Heikkinen R, Toiviainen-Salo S, Henriksson M, Puukko-Viertomies LR, Jahnukainen K. Long-term skeletal consequences of childhood acute lymphoblastic leukemia in adult males: a cohort study. Eur J Endocrinol. 2013;168:281–288.
    1. Mandel K, Atkinson S, Barr RD, Pencharz P. Skeletal morbidity in childhood acute lymphoblastic leukemia. J Clin Oncol. 2004;22:1215–1221.
    1. Maniadaki I, Stiakaki E, Germanakis I, Kalmanti M. Evaluation of bone mineral density at different phases of therapy of childhood all. Pediatr Hematol Oncol. 2006;23:11–18.
    1. Janiszewski PM, Oeffinger KC, Church TS, et al. Abdominal obesity, liver fat, and muscle composition in survivors of childhood acute lymphoblastic leukemia. J Clin Endocrinol Metab. 2007;92:3816–3821.
    1. Ness KK, Baker KS, Dengel DR, et al. Body composition, muscle strength deficits and mobility limitations in adult survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2007;49:975–981.
    1. Harila-Saari AH, Huuskonen UE, Tolonen U, Vainionpaa LK, Lanning BM. Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials. Med Pediatr Oncol. 2001;36:345–351.
    1. Lehtinen SS, Huuskonen UE, Harila-Saari AH, Tolonen U, Vainionpaa LK, Lanning BM. Motor nervous system impairment persists in long-term survivors of childhood acute lymphoblastic leukemia. Cancer. 2002;94:2466–2473.
    1. Ramchandren S, Leonard M, Mody RJ, et al. Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. J Peripher Nerv Syst. 2009;14:184–189.
    1. Bar G, Black PC, Gutjahr P, Stopfkuchen H. Recovery kinetics of heart rate and oxygen uptake in long-term survivors of acute leukemia in childhood. Eur J Pediatr. 2007;166:1135–1142.
    1. Jarvela LS, Niinikoski H, Lahteenmaki PM, et al. Physical activity and fitness in adolescent and young adult long-term survivors of childhood acute lymphoblastic leukaemia. J Cancer Surviv. 2010;4:339–345.
    1. Tonorezos ES, Snell PG, Moskowitz CS, et al. Reduced cardiorespiratory fitness in adult survivors of childhood acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013
    1. van Brussel M, Takken T, van der Net J, et al. Physical function and fitness in long-term survivors of childhood leukaemia. Pediatr Rehabil. 2006;9:267–274.
    1. Warner JT, Bell W, Webb DK, Gregory JW. Daily energy expenditure and physical activity in survivors of childhood malignancy. Pediatr Res. 1998;43:607–613.
    1. Jarfelt M, Fors H, Lannering B, Bjarnason R. Bone mineral density and bone turnover in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol. 2006;154:303–309.
    1. Joyce ED, Nolan VG, Ness KK, et al. Association of muscle strength and bone mineral density in adult survivors of childhood acute lymphoblastic leukemia. Arch Phys Med Rehabil. 2011;92:873–879.
    1. Tillmann V, Darlington AS, Eiser C, Bishop NJ, Davies HA. Male sex and low physical activity are associated with reduced spine bone mineral density in survivors of childhood acute lymphoblastic leukemia. J Bone Miner Res. 2002;17:1073–1080.
    1. Alos N, Grant RM, Ramsay T, et al. High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol. 2012;30:2760–2767.
    1. Diessel E, Fuerst T, Njeh CF, et al. Evaluation of a new body composition phantom for quality control and cross calibration of DXA devices. J Appl Physiol. 2000;89:599–605.
    1. Kalender WA. A phantom for standardization and quality control in spinal bone mineral measurements by QCT and DXA: design considerations and specifications. Med Phys. 1992;19:583–586.
    1. Kalender WA, Felsenberg D, Genant HK, Fischer M, Dequeker J, Reeve J. The European Spine Phantom - a tool for standardization and quality control in spinal bone mineral measurements by DXA and QCT. Eur J Radiol. 1995;20:83–92.
    1. Molgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF. Whole body bone mineral content in healthy children and adolescents. Arch Dis Child. 1997;76:9–15.
    1. Orwoll ES, Oviatt SK, Biddle JA. Precision of dual-energy x-ray absorptiometry: development of quality control rules and their application in longitudinal studies. J Bone Miner Res. 1993;8:693–699.
    1. Zemel BS, Leonard MB, Kelly A, et al. Height adjustment in assessing dual energy x-ray absorptiometry measurements of bone mass and density in children. J Clin Endocrinol Metab. 2010;95:1265–1273.
    1. Centers for Disease Control and Prevention . A SAS Program for the CDC Growth Charts. Atlanta, GA: Mar 26, 2014. [cited 2014 May 8]. Available from: .
    1. Marchese VG, Chiarello LA, Lange BJ. Effects of physical therapy intervention for children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2004;42:127–133.
    1. Soucie JM, Wang C, Forsyth A, et al. Range of motion measurements: reference values and a database for comparison studies. Haemophilia. 2011;17:500–507.
    1. Eek MN, Kroksmark AK, Beckung E. Isometric muscle torque in children 5 to 15 years of age: normative data. Arch Phys Med Rehabil. 2006;87:1091–1099.
    1. Merlini L, Mazzone ES, Solari A, Morandi L. Reliability of hand-held dynamometry in spinal muscular atrophy. Muscle Nerve. 2002;26:64–70.
    1. Hager-Ross C, Rosblad B. Norms for grip strength in children aged 4–16 years. Acta Paediatr. 2002;91:617–625.
    1. Mathiowetz V, Wiemer DM, Federman SM. Grip and pinch strength: norms for 6-to 19-year olds. Am J Occup Ther. 1986;40:705–711.
    1. Bruininks RH, Bruininks BD. BOT2 Bruininks-Oseretsky Test of Motor Proficiency. AGS Publishing; Circle Pines, MN: 2005.
    1. Geiger R, Strasak A, Treml B, et al. Six-minute walk test in children and adolescents. J Pediatr. 2007;150:395–399.
    1. Russell KM, Hudson M, Long A, Phipps S. Assessment of health-related quality of life in children with cancer: consistency and agreement between parent and child reports. Cancer. 2006;106:2267–2274.
    1. Landgraf JM, Abetz L, Ware JE. Child Health questionnaire (CHQ): A User's Manual. HealthAct; Boston, MA: 1999.
    1. Halton JM, Atkinson SA, Fraher L, et al. Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia. J Bone Miner Res. 1996;11:1774–1783.
    1. Rayar MS, Nayiager T, Webber CE, Barr RD, Athale UH. Predictors of bony morbidity in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2012;59:77–82.
    1. Riccio I, Marcarelli M, Del Regno N, et al. Musculoskeletal problems in pediatric acute leukemia. J Pediatr Orthop B. 2013;22:264–269.
    1. van der Sluis IM, van den Heuvel-Eibrink MM, Hahlen K, Krenning EP, de Muinck Keizer-Schrama SM. Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia. J Pediatr. 2002;141:204–210.
    1. Swiatkiewicz V, Wysocki M, Odrowaz-Sypniewska G, Koltan A, Manysiak S, Dylewska K. Bone mass and bone mineral metabolism at diagnosis and after intensive treatment in children with acute lymphoblastic leukemia. Med Pediatr Oncol. 2003;41:578–580.
    1. Halton J, Gaboury I, Grant R, et al. Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res. 2009;24:1326–1334.
    1. Atkinson SA, Halton JM, Bradley C, Wu B, Barr RD. Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: influence of disease, drugs and nutrition. Int J Cancer Suppl. 1998;11:35–39.
    1. Aldhafiri FK, McColl JH, Reilly JJ. Prevalence of being underweight and overweight and obesity at diagnosis in UK patients with childhood acute lymphoblastic leukaemia 1985–2002. J Hum Nutr Diet. 2013
    1. Esbenshade AJ, Simmons JH, Koyama T, Koehler E, Whitlock JA, Friedman DL. Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer. 2011;56:372–378.
    1. Ruiz JC, Mandel C, Garabedian M. Influence of spontaneous calcium intake and physical exercise on the vertebral and femoral bone mineral density of children and adolescents. J Bone Miner Res. 1995;10:675–682.
    1. Au LE, Rogers GT, Harris SS, Dwyer JT, Jacques PF, Sacheck JM. Associations of vitamin D intake with 25-hydroxyvitamin D in overweight and racially/ethnically diverse US children. J Acad Nutr Diet. 2013;113:1511–1516.
    1. Ness KK, Hudson MM, Pui CH, et al. Neuromuscular impairments in adult survivors of childhood acute lymphoblastic leukemia: associations with physical performance and chemotherapy doses. Cancer. 2012;118:828–838.
    1. Tan SY, Poh BK, Nadrah MH, Jannah NA, Rahman J, Ismail MN. Nutritional status and dietary intake of children with acute leukaemia during induction or consolidation chemotherapy. J Hum Nutr Diet. 2013
    1. Chow EJ, Pihoker C, Hunt K, Wilkinson K, Friedman DL. Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer. 2007;110:2313–2320.
    1. Chow EJ, Pihoker C, Friedman DL, et al. Glucocorticoids and insulin resistance in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2013;60:621–626.
    1. Orgel E, Sposto R, Malvar J, et al. Impact on Survival and Toxicity by Duration of Weight Extremes During Treatment for Pediatric Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group. J Clin Oncol. 2014
    1. Gurney JG, Ness KK, Sibley SD, et al. Metabolic syndrome and growth hormone deficiency in adult survivors of childhood acute lymphoblastic leukemia. Cancer. 2006;107:1303–1312.
    1. Oeffinger KC, Adams-Huet B, Victor RG, et al. Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol. 2009;27:3698–3704.
    1. Steinberger J, Sinaiko AR, Kelly AS, et al. Cardiovascular risk and insulin resistance in childhood cancer survivors. J Pediatr. 2012;160:494–499.
    1. Tonorezos ES, Vega GL, Sklar CA, et al. Adipokines, body fatness, and insulin resistance among survivors of childhood leukemia. Pediatr Blood Cancer. 2012;58:31–36.
    1. Rayar M, Webber CE, Nayiager T, Sala A, Barr RD. Sarcopenia in children with acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2013;35:98–102.
    1. Kameda G, Vieker S, Duck C, Blaes F, Langler A. Paraneoplastic myopathy as a very rare manifestation of acute lymphoblastic leukemia. Klin Padiatr. 2010;222:386–387.
    1. Gocha Marchese V, Chiarello LA, Lange BJ. Strength and functional mobility in children with acute lymphoblastic leukemia. Med Pediatr Oncol. 2003;40:230–232.
    1. Bindels LB, Beck R, Schakman O, et al. Restoring specific lactobacilli levels decreases inflammation and muscle atrophy markers in an acute leukemia mouse model. PLoS One. 2012;7:e37971.
    1. Menconi M, Fareed M, O'Neal P, Poylin V, Wei W, Hasselgren PO. Role of glucocorticoids in the molecular regulation of muscle wasting. Crit Care Med. 2007;35:S602–608.

Source: PubMed

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