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The association between glucocorticoid therapy and BMI z-score changes in children with acute lymphoblastic leukemia

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Abstract

Purpose

Few studies have addressed the common issue of weight gain in children with acute lymphoblastic leukemia (ALL) during early phases of treatment, and even fewer have used the appropriate measure for weight fluctuation in children, BMI-for-age z-scores (BAZs). The purpose of this study is thus to measure the extent of the weight gain in BAZ during the 150 first days of treatment and to identify factors associated with the weight gain. Furthermore, we wish to raise the question of whether changes in treatment protocols automatically should be followed by an evaluation of the nutritional guidelines.

Method

In this retrospective study, the medical records of 51 children with ALL treated with the NOPHO ALL 2008 protocol at Copenhagen University Hospital were assessed. Patient characteristics were extracted, and height, weight, and age during the first 150 days of treatment were converted to BAZ.

Results

During 150 days of treatment, the proportion of overweight/obese patients increased significantly from 9.8 to 33.3 %. The mean change in BAZ (∆BAZ) was +1 standard deviation (0.02 ± 1.16 vs. 1.12 ± 1.44; p < 0.001) and BAZ increased significantly during periods with glucocorticoid (GC) treatment but not in periods without GC. ΔBAZ was larger in boys compared to girls, and ΔBAZ was higher in patients who were under/normal weight at diagnosis, compared to patients who were overweight/obese (1.26 ± 1.29 vs. −0.04 ± 0.41; p = 0.032).

Conclusion

BAZ increased significantly in children with ALL during the initial treatment with the NOPHO ALL 2008 protocol. This is likely associated with the GC administration and influenced by gender and initial BAZ.

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References

  1. National Cancer Institute, US National Institutes of Health (2014) General Information About Childhood Acute Lymphoblastic Leukemia (ALL). http://www.cancer.gov/cancertopics/pdq/treatment/childALL/HealthProfessional. Accessed 5 March 2014

  2. Smith MA, Seibel NL, Altekruse SF et al (2010) Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28:2625–2634

    Article  PubMed Central  PubMed  Google Scholar 

  3. Pui CH, Gajjar AJ, Kane JR et al (2011) Challenging issues in pediatric oncology. Nat Rev Clin Oncol 8:540–549

    Article  PubMed Central  PubMed  Google Scholar 

  4. Kawedia JD, Kaste SC, Pei D et al (2011) Pharmacokinetic, pharmacodynamic, and pharmacogenetic determinants of osteonecrosis in children with acute lymphoblastic leukemia. Blood 117:2340–2347

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Pession A, Valsecchi MG, Masera G et al (2005) Long-term results of a randomized trial on extended use of high dose L-asparaginase for standard risk childhood acute lymphoblastic leukemia. J Clin Oncol 23:7161–7167

    Article  CAS  PubMed  Google Scholar 

  6. Chow EJ, Pihoker C, Friedman DL et al (2013) Glucocorticoids and insulin resistance in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 60:621–626

    Article  PubMed Central  PubMed  Google Scholar 

  7. Frandsen TL, Heyman M, Abrahamsson J et al (2013) Complying with the European Clinical Trials directive while surviving the administrative pressure—an alternative approach to toxicity registration in a cancer trial. Eur J Cancer 50:251–259

    Article  PubMed  Google Scholar 

  8. Gross KL, Cidlowski JA (2008) Tissue-specific glucocorticoid action: a family affair. Trends Endocrinol Metab 9:331–339

    Article  Google Scholar 

  9. Iughetti L, Bruzzi P, Predieri B, Paolucci P (2012) Obesity in patients with acute lymphoblastic leukemia in childhood. Ital J Pediatr 38:1–11

    Article  Google Scholar 

  10. Bernbeck B, Christaras A, Krauth K et al (2004) Bone marrow oedema and aseptic osteonecrosis in children and adolescents with acute lymphoblastic leukaemia or non-Hodgkin-lymphoma treated with hyperbaric-oxygen-therapy (HBO): an approach to cure?—BME/AON and hyperbaric oxygen therapy as a treatment modality. Klin Padiatr 216:370–378

    Article  CAS  PubMed  Google Scholar 

  11. Daniels SR, Arnett DK, Eckel RH et al (2010) Overweight in children and adolescents pathophysiology, consequences, prevention, and treatment. Circulation 111:1999–2012

    Article  Google Scholar 

  12. Ethier MC, Alexander S, Abla O et al (2012) Association between obesity at diagnosis and weight change during induction and survival in pediatric acute lymphoblastic leukemia. Leuk Lymphoma 53:1677–1681

    Article  PubMed  Google Scholar 

  13. Butturini AM, Dorey FJ, Lange BJ et al (2007) Obesity and outcome in pediatric acute lymphoblastic leukemia. J Clin Oncol 25:2063–2069

    Article  PubMed  Google Scholar 

  14. Orgel E, Sposto R, Malvar J et al (2014) 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 32:1331–1337

    Article  PubMed Central  PubMed  Google Scholar 

  15. Royal College of Nursing. Nutrition in children and young people with cancer—RCN guidance (2010) http://www.rcn.org.uk/__data/assets/pdf_file/0010/338689/003805.pdf. Accessed 20 Aug 2014

  16. Möricke A, Zimmermann M, Reiter A et al (2010) Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia 24:265–284

    Article  PubMed  Google Scholar 

  17. Vora A, Mitchell C, Rowntree C, et al. (2011) Guidelines for treatment of children and young persons with acute lymphoblastic leukaemia and lymphoblastic lymphoma. https://www.ctsu.ox.ac.uk/research/mega-trials/leukaemia-trials/ukall-2003/interim-guidelines. Accessed 17 July 2014

  18. Silverman LB, Stevenson KE, O'Brien JE et al (2010) Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1985-2000). Leukemia 24:320–334

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Toft N, Birgens H, Abrahamsson J et al (2013) Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol. Eur J Haematol 90:404–412

    Article  PubMed  Google Scholar 

  20. Dalton VK, Rue M, Silverman LB et al (2003) Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment. J Clin Oncol 21:2953–2960

    Article  PubMed  Google Scholar 

  21. World Health Organization. Child growth standards. http://www.who.int/childgrowth/software/en/. Accessed 1 Mar 2013

  22. Brunning RD, Borowitz M, Matutes E et al (2001) Precursor B-cell and T-cell neoplasms. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds) World health organization classification of tumors—tumours of haematopoietic and lymphoid tissues. IARCPress Inc, Lyon, pp 109–117

    Google Scholar 

  23. Hjalgrim LL, Rostgaard K, Schmiegelov K et al (2003) Age- and sex-specific incidence of childhood leukemia by immunophenotype in the Nordic countries. J Natl Cancer Inst 95:1539–1544

    Article  PubMed  Google Scholar 

  24. Larsen LM, Hertel NT, Mølgaard C et al (2012) Prevalence of overweight and obesity in Danish preschool children over a 10-year period: a study of two birth cohorts in general practice. Acta Paediatr 101:201–207

    Article  PubMed  Google Scholar 

  25. Statistics Denmark. Immigrants and their descendents. http://www.dst.dk/en/Statistik/emner/indvandrere-og-efterkommere/indvandrere-og-efterkommere.aspx. Accessed 9 May 2013

  26. WHO. A healthy lifestyle—body mass index—BMI, World Health Organisation—Regional office for Europe. http://www.euro.who.int/en/what-we-do/health-topics/disease-prevention/nutrition/a-healthy-lifestyle/body-mass-index-bmi. Accessed 22 Apr 2013

  27. Esbenshade AJ, Simmons JH, Koyama T et al (2011) Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 56:372–378

    Article  PubMed Central  PubMed  Google Scholar 

  28. Withycombe JS, Post‐White JE, Meza JL et al (2009) Weight patterns in children with higher risk ALL: a report from the Children's Oncology Group (COG) for CCG 1961. Pediatr Blood Cancer 53:1249–1254

    Article  PubMed Central  PubMed  Google Scholar 

  29. Chow EJ, Pihoker C, Hunt K et al (2007) Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer 110:2313–2320

    Article  PubMed  Google Scholar 

  30. Rang HP, Dale MM, Ritter JM et al (2012) Rang and Dales's pharmacology. Elsevier, Spain

    Google Scholar 

  31. Tomlinson JW, Walker EA, Bujalska IJ et al (2004) 11-beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocr Rev 25:831–866

    Article  CAS  PubMed  Google Scholar 

  32. Bagamasbad P, Denver RJ (2011) Mechanisms and significance of nuclear receptor auto- and cross-regulation. Gen Comp Endocrinol 170:3–17

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Pui CH, Robison LL, Look AT (2008) Acute lymphoblastic leukaemia. Lancet 371:1030–1043

    Article  CAS  PubMed  Google Scholar 

  34. Tyc VL, Mulhern RK, Fairclough D et al (1993) Chemotherapy induced nausea and emesis in pediatric cancer patients: external validity of child and parent emesis ratings. J Dev Behav Pediatr 14:236–241

    Article  CAS  PubMed  Google Scholar 

  35. Schacke H, Docke WD, Asadullah K (2002) Mechanisms involved in the side effects of glucocorticoids. Pharmacol Ther 96:23–43

    Article  CAS  PubMed  Google Scholar 

  36. Jansen H, Postma A, Stolk RP, Kamps WA (2009) Acute lymphoblastic leukemia and obesity: increased energy intake or decreased physical activity? Support Care Cancer 17:103–106

    Article  CAS  PubMed  Google Scholar 

  37. Reilly JJ, Brougham M, Montgomery C et al (2001) Effect of glucocorticoid therapy on energy intake in children treated for acute lymphoblastic leukemia. J Clin Endocrinol Metab 86:3742–3745

    Article  CAS  PubMed  Google Scholar 

  38. Lim CT, Kola B, Korbonits M (2010) AMPK as a mediator of hormonal signalling. J Mol Endocrinol 44:87–97

    Article  CAS  PubMed  Google Scholar 

  39. Pritchard LE, Turnbull AV, White A (2002) Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol 172:411–421

    Article  CAS  PubMed  Google Scholar 

  40. Spencer SJ, Tilbrook A (2011) The glucocorticoid contribution to obesity. Stress 14:233–246

    CAS  PubMed  Google Scholar 

  41. Peckett AJ, Wright DC, Ridell MC (2011) The effects of glucocorticoids on adipose tissue lipid metabolism. Metabolism 60:1500–1510

    Article  CAS  PubMed  Google Scholar 

  42. Arnaldi G, Scandali VM, Trementino L et al (2010) Pathophysiology of dyslipidemia in Cushing’s syndrome. Neuroendocrinology 92:86–90

    Article  CAS  PubMed  Google Scholar 

  43. Pereira RMR, Freire de Carvalho J (2011) Glucocorticoid-induced myopathy. Jt Bone Spine 78:41–44

    Article  CAS  Google Scholar 

  44. Schakman O, Gilson H, Kalista S, Thissen J (2009) Mechanisms of muscle atrophy induced by glucocorticoids. Horm Res Paediatr 72:36–41

    Article  CAS  Google Scholar 

  45. Mauras N (2009) Can growth hormone counteract the catabolic effects of steroids? Horm Res Paediatr 72:48–54

    Article  CAS  Google Scholar 

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Correspondence to Thomas Leth Frandsen.

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Arpe, ML.H., Rørvig, S., Kok, K. et al. The association between glucocorticoid therapy and BMI z-score changes in children with acute lymphoblastic leukemia. Support Care Cancer 23, 3573–3580 (2015). https://doi.org/10.1007/s00520-015-2718-5

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  • DOI: https://doi.org/10.1007/s00520-015-2718-5

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