Home Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia
Article
Licensed
Unlicensed Requires Authentication

Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia

  • Sarah Elitzur , Revital Houri-Shtrecher , Michal Yackobovitz-Gavan , Galia Avrahami , Shlomit Barzilai , Gil Gilad , Yael Lebenthal , Moshe Phillip , Batia Stark , Isaac Yaniv and Shlomit Shalitin EMAIL logo
Published/Copyright: July 25, 2017
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 30 Issue 8

Abstract

Background:

Survivors of acute lymphoblastic leukemia (ALL) may experience endocrine dysfunction. This study evaluated growth and pubertal patterns in survivors of childhood ALL.

Methods:

Longitudinal assessment of anthropometric measurements and pubertal status was performed in a retrospective cohort of survivors (n=183). Median age at last endocrine visit was 16.1 years (range 8.2–27.6); median follow-up time was 8.7 years (range 3–21.4).

Results:

Treatment with chemotherapy+prophylactic cranial radiation (pCRT, n=29) was associated with lower mean height standard deviation score (SDS) than chemotherapy alone (n=154) (p=0.001) and higher prevalence of adult short stature (13% vs. 2.2%). Mean age at pubertal onset was normal (girls: 10.3±1.3 years; boys: 12.0±1.3 years). Precocious puberty, diagnosed in 8.7% of patients, was more prevalent in pCRT-treated girls. Rates of overweight and obesity were 22.9% and 9.3%, respectively. Predictors of endocrine disorders were pCRT (p=0.031) and female gender (p=0.041); of obesity, higher body mass index (BMI)-SDS at diagnosis (p=0.001); and of short stature, lower height-SDS at diagnosis (p=0.038).

Conclusions:

Most childhood ALL survivors given chemotherapy alone attain normal adult height and puberty. Childhood ALL survivors are at increased risk of overweight, especially those with increased BMI at diagnosis. Clinicians should screen for overweight early in survivorship and introduce early interventions.

Keywords: acute lymphoblastic leukemia; growth; obesity; puberty; survivors
Corresponding author: Professor Shlomit Shalitin, MD, The Jesse Z. and Lea Shafer Institute for Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, 14 Kaplan Street, Petach Tikva 4920235, Israel, Phone: +972-3-925-3282, Fax: +972-3-925-3836
Sarah Elitzur and Revital Huri-Shtrecher contributed equally to this work.

Acknowledgments

The authors wish to thank Gloria Ginzach for editorial assistance.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med 2015;373:1541–52.10.1056/NEJMra1400972Search in Google Scholar PubMed

2. Pui CH, Mullighan CG, Evans WE, Relling MV. Pediatric acute lymphoblastic leukemia: where are we going and how do we get there? Blood 2012;120:1165–74.10.1182/blood-2012-05-378943Search in Google Scholar PubMed PubMed Central

3. Mody R, Li S, Dover DC, Sallan S, Leisenring W, et al. Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Blood 2008;111:5515–23.10.1182/blood-2007-10-117150Search in Google Scholar PubMed PubMed Central

4. Pui CH, Cheng C, Leung W, Rai SN, Rivera GK, et al. Extended follow-up of long-term survivors of childhood acute lymphoblastic leukemia. N Engl J Med 2003;349:640–9.10.1056/NEJMoa035091Search in Google Scholar PubMed

5. Esbenshade AJ, Simmons JH, Koyama T, Koehler E, Whitlock JA, et al. Body mass index and blood pressure changes over the course of treatment of pediatric acute lymphoblastic leukemia. Pediatr Blood Cancer 2011;56:372–8.10.1002/pbc.22782Search in Google Scholar PubMed PubMed Central

6. Nysom K, Holm K, Michaelsen KF, Hertz H, Muller J, et al. Degree of fatness after treatment for acute lymphoblastic leukemia in childhood. J Clin Endocrinol Metab 1999;84:4591–6.10.1210/jc.84.12.4591Search in Google Scholar

7. Oeffinger KC, Adams-Huet B, Victor RG, Church TS, Snell PG, et al. Insulin resistance and risk factors for cardiovascular disease in young adult survivors of childhood acute lymphoblastic leukemia. J Clin Oncol 2009;27:3698–704.10.1200/JCO.2008.19.7251Search in Google Scholar PubMed PubMed Central

8. Hudson MM. Late complications after leukemia therapy. In: Pui C-H, editor. Childhood leukemias, 3rd ed. New York: Cambridge University Press, 2012:701–22.10.1017/CBO9780511977633.031Search in Google Scholar

9. Frisk P, Arvidson J, Gustafsson J, Lönnerholm G. Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia. Bone Marrow Transplant 2004;33:205–10.10.1038/sj.bmt.1704324Search in Google Scholar PubMed

10. Geenen MM, Cardous-Ubbink MC, Kremer LC, van den Bos C, van der Pal HJ, et al. Medical assessment of adverse health outcomes in long-term survivors of childhood cancer. J Am Med Assoc 2007;297:2705–15.10.1001/jama.297.24.2705Search in Google Scholar PubMed

11. Hokken-Koelega AC, van Doorn JW, Hählen K, Stijnen T, de Muinck Keizer-Schrama SM, et al. Long-term effects of treatment for acute lymphoblastic leukemia with and without cranial irradiation on growth and puberty: a comparative study. Pediatr Res 1993;33:577–82.10.1203/00006450-199306000-00008Search in Google Scholar

12. Ogilvy-Stuart AL, Clayton PE, Shalet SM. Cranial irradiation and early puberty. J Clin Endocrinol Metab 1994;78:1282–6.Search in Google Scholar

13. Woodward E, Jessop M, Glaser A, Stark D. Late effects in survivors of teenage and young adult cancer: does age matter? Ann Oncol 2011;22:2561–8.10.1093/annonc/mdr044Search in Google Scholar

14. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 2009;360:2730–41.10.1056/NEJMoa0900386Search in Google Scholar

15. Stark B, Sharon R, Attias D, Balin A, Cividalli G, et al. Effective preventive central nervous system therapy with extended triple intrathecal therapy and the modified ALL-BFM 86 chemotherapy program in an enlarged non-high risk group of children and adolescents with non-B-cell acute lymphoblastic leukemia: the Israel National Study report. Cancer 2000;88:205–14.10.1002/(SICI)1097-0142(20000101)88:1<205::AID-CNCR28>3.0.CO;2-7Search in Google Scholar

16. Stark B, Avrahami G, Nirel R, Abramov A, Attias D, et al. Extended triple intrathecal therapy in children with T-cell acute lymphoblastic leukaemia: a report from the Israeli National ALL-Studies. Br J Haematol 2009;147:113–24.10.1111/j.1365-2141.2009.07853.xSearch in Google Scholar

17. Stark B, Nirel R, Avrahami G, Abramov A, Attias D, et al. Long-term results of the Israeli National Studies in childhood acute lymphoblastic leukemia: INS 84, 89 and 98. Leukemia 2010;24:419–24.10.1038/leu.2009.254Search in Google Scholar

18. Möricke A, Zimmermann M, Reiter A, Henze G, Schrauder A, et al. Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000. Leukemia 2010;24:265–84.10.1038/leu.2009.257Search in Google Scholar

19. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Arch Dis Child 1969;44:291–303.10.1136/adc.44.235.291Search in Google Scholar

20. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:12–23.10.1136/adc.45.239.13Search in Google Scholar

21. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, et al. CDC growth charts: United States. Adv Data 2000;8:1–27.Search in Google Scholar

22. Rosenfield R. Puberty in the female and its disorders. In: Sperling MA, editor. Pediatric Endocrinology, 2nd ed. Philadelphia: Elsevier Science, 2002: 494.Search in Google Scholar

23. Styne DM. The Testes: disorders of sexual differentiation and puberty in the male. In: Sperling MA, editor. Pediatric endocrinology, 2nd ed. Philadelphia: Elsevier Science, 2002: 599.Search in Google Scholar

24. Katz JA, Pollock BH, Jacaruso D, Morad A. Final attained height in patients successfully treated for childhood acute lymphoblastic leukemia. J Pediatr 1993;123:546–52.10.1016/S0022-3476(05)80948-5Search in Google Scholar

25. Stubberfield TG, Byrne GC, Jones TW. Growth and growth hormone secretion after treatment for acute lymphoblastic leukemia in childhood. 18-Gy versus 24-Gy cranial irradiation. J Pediatr Hematol Oncol 1995;17:167–71.10.1097/00043426-199505000-00012Search in Google Scholar PubMed

26. Jaruratanasirikul S, Owasith K, Wongchanchailert M, Laosombat V, Sriplung H. Growth patterns and final height of survivors of childhood leukemia. J Pediatr Endocrinol Metab 2004;17:719–26.10.1515/JPEM.2004.17.5.719Search in Google Scholar PubMed

27. Hata M, Ogino I, Aida N, Saito K, Omura M, et al. Prophylactic cranial irradiation of acute lymphoblastic leukemia in childhood: outcomes of late effects on pituitary function and growth in long-term survivors. Int J Cancer 2001;96 (Suppl):117–24.10.1002/ijc.10348Search in Google Scholar PubMed

28. Melin AE, Adan L, Leverger G, Souberbielle JC, Schaison G, et al. Growth hormone secretion, puberty and adult height after cranial irradiation with 18 Gy for leukaemia. Eur J Pediatr 1998;157:703–7.10.1007/s004310050918Search in Google Scholar PubMed

29. Groot-Loonen JJ, van Setten P, Otten BJ, van’t Hof MA, Lippens RJ, et al. Shortened and diminished pubertal growth in boys and girls treated for acute lymphoblastic leukaemia. Acta Paediatr 1996;85:1091–5.10.1111/j.1651-2227.1996.tb14223.xSearch in Google Scholar PubMed

30. Leiper AD, Stanhope R, Kitching P, Chessells JM. Precocious and premature puberty associated with treatment of acute lymphoblastic leukaemia. Arch Dis Child 1987;62:1107–12.10.1136/adc.62.11.1107Search in Google Scholar PubMed PubMed Central

31. Oberfield SE, Sklar CA. Endocrine sequelae in survivors of childhood cancer. Adolesc Med 2002;13:161–9.Search in Google Scholar

32. Vandecruys E, Dhooge C, Craen M, Benoit Y, De Schepper J. Longitudinal linear growth and final height is impaired in childhood acute lymphoblastic leukemia survivors after treatment without cranial irradiation. J Pediatr 2013;163:268–73.10.1016/j.jpeds.2012.12.037Search in Google Scholar PubMed

33. Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, et al. Decreased adult height in survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Pediatr 2007;150:370–5.10.1016/j.jpeds.2006.11.036Search in Google Scholar PubMed PubMed Central

34. Dalton VK, Rue M, Silverman LB, Gelber RD, Asselin BL, et al. Height and weight in children treated for acute lymphoblastic leukemia: relationship to CNS treatment. J Clin Oncol 2003;21:2953–60.10.1200/JCO.2003.03.068Search in Google Scholar PubMed

35. Breene RA, Williams RM, Hartle J, Gattens M, Acerini CL, et al. Auxological changes in UK survivors of childhood acute lymphoblastic leukaemia treated without cranial irradiation. Br J Cancer 2011;104:746–9.10.1038/bjc.2011.16Search in Google Scholar PubMed PubMed Central

36. Chow EJ, Pihoker C, Hunt K,Wilkinson K, Friedman DL.Obesity and hypertension among children after treatment for acute lymphoblastic leukemia. Cancer 2007;110:2313–20.10.1002/cncr.23050Search in Google Scholar

37. Dacou-Voutetakis C, Kitra V, Grafakos S, Polychronopoulou S, Drakopoulou M, et al. Auxologic data and hormonal profile in long-term survivors of childhood acute lymphoid leukemia. Am J Pediatr Hematol Oncol 1993;15:277–83.Search in Google Scholar

38. Didi M, Didcock E, Davies HA, Ogilvy-Stuart AL, Wales JK, et al. High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood. J Pediatr 1995;127:63–7.10.1016/S0022-3476(95)70258-XSearch in Google Scholar

39. Garmey EG, Liu Q, Sklar CA, Meacham LR, Mertens AC, et al. Longitudinal changes in obesity and body mass index among adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. J Clin Oncol 2008;26:4639–45.10.1200/JCO.2008.16.3527Search in Google Scholar

40. Zhang FF, Kelly MJ, Saltzman E, Must A, Roberts SB, et al. Obesity in pediatric ALL survivors: a meta-analysis. Pediatrics 2014;133:e704–15.10.1542/peds.2013-3332Search in Google Scholar

41. Zhang FF, Liu S, Chung M, Kelly MJ. Growth patterns during and after treatment in patients with pediatric ALL: a meta-analysis. Pediatr Blood Cancer 2015;62:1452–60.10.1002/pbc.25519Search in Google Scholar

42. Sklar CA, Mertens AC, Walter A, Mitchell D, Nesbit ME, et al. Changes in body mass index and prevalence of overweight in survivors of childhood acute lymphoblastic leukemia: role of cranial irradiation. Med Pediatr Oncol 2000;35:91–5.10.1002/1096-911X(200008)35:2<91::AID-MPO1>3.0.CO;2-GSearch in Google Scholar

43. Karaman S, Ercan O, Yildiz I, Bolayirli M, Celkan T, et al. Late effects of childhood ALL treatment on body mass index and serum leptin levels. J Pediatr Endocrinol Metab 2010;23:669–74.10.1515/JPEM.2010.23.7.669Search in Google Scholar

44. Harper RL, Breene RA, Gattens M, Williams RM, Murray MJ. Non-irradiated female survivors of childhood acute lymphoblastic leukaemia are at risk of long-term increases in weight and body mass index. Br J Haematol 2013;163:510–3.10.1111/bjh.12552Search in Google Scholar

45. Lindemulder SJ, Stork LC, Bostrom B, Lu X, Devidas M, et al. Survivors of standard risk acute lymphoblastic leukemia do not have increased risk for overweight and obesity compared to non-cancer peers: a report from the Children’s Oncology Group. Pediatr Blood Cancer 2015;62:1035–41.10.1002/pbc.25411Search in Google Scholar

46. Rabinowicz M (June 18, 2009) Overweight and Obesity: Review of the Situation in Israel. http://www.knesset.gov.il/mmm/data/pdf/m02303.pdf. [Article in Hebrew]Search in Google Scholar

47. World Health Organization. Inequalities in Young People’s Health: HBSC International Report from the 2005/2006 Survey. http://www.euro.who.int/datapublications/Publications/Catalogue/20080616_1 Accessed May 27, 2009.Search in Google Scholar

48. Razzouk BI, Rose SR, Hongeng S, Wallace D, Smeltzer MP, et al. Obesity in survivors of childhood acute lymphoblastic leukemia and lymphoma. J Clin Oncol 2007;25:1183–9.10.1200/JCO.2006.07.8709Search in Google Scholar

49. Zhang FF, Rodday AM, Kelly MJ, Must A, MacPherson C, et al. Predictors of being overweight or obese in survivors of pediatric acute lymphoblastic leukemia (ALL). Pediatr Blood Cancer 2014;61:1263–9.10.1002/pbc.24960Search in Google Scholar

50. Davies HA, Didcock E, Didi M, Ogilvy-Stuart A, Wales JK, et al. Growth, puberty and obesity after treatment for leukaemia. Acta Paediatr 1995;(Suppl 411):45–50.10.1111/j.1651-2227.1995.tb13862.xSearch in Google Scholar

51. Didcock E, Davies HA, Didi M, Ogilvy Stuart AL, Wales JK, et al. Pubertal growth in young adult survivors of childhood leukemia. J Clin Oncol 1995;13:2503–7.10.1200/JCO.1995.13.10.2503Search in Google Scholar

52. Chow EJ, Friedman DL, Yasui Y, Whitton JA, Stovall M, et al. Timing of menarche among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study. Pediatr Blood Cancer 2008;50:854–8.10.1002/pbc.21316Search in Google Scholar

53. Mills JL, Fears TR, Robison LL, Nicholson HS, Sklar CA, et al. Menarche in a cohort of 188 long-term survivors of acute lymphoblastic leukemia. J Pediatr 1997;131:598–602.10.1016/S0022-3476(97)70069-6Search in Google Scholar

54. Jarfelt M, Lannering B, Bosaeus I, Johannsson G, Bjarnason R. Body composition in young adult survivors of childhood acute lymphoblastic leukaemia. Eur J Endocrinol 2005;153:81–9.10.1530/eje.1.01931Search in Google Scholar PubMed

Received: 2017-3-6
Accepted: 2017-6-26
Published Online: 2017-7-25
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Endocrine aspects in cystic fibrosis
  4. Original Articles
  5. A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis
  6. Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function
  7. Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of <0.3 units/kg/day to the gold standard insulin-dose adjusted hemoglobin A1c of ≤9 for the detection of partial clinical remission
  8. Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome
  9. Parent reported nutritional risk and laboratory indices of cardiometabolic risk and in preschool-aged children
  10. Multinodular goiter in children: treatment controversies
  11. Atopy as a risk factor for subclinical hypothyroidism development in children
  12. Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism
  13. Health-related quality of life among children with Turner syndrome: controlled cross-sectional study
  14. Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia
  15. Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening
  16. Letter to the Editor
  17. Sensitivity and specificity of cystic fibrosis-related diabetes screening methods: which test should be the reference method?
  18. Case Reports
  19. Type 1 rhizomelic chondrodysplasia punctata with a homozygous PEX7 mutation
  20. Severe hypertriglyceridemia at new onset type 1 diabetes mellitus
  21. 45,X/46,XY ovotesticular disorder of sex development revisited: undifferentiated gonadal tissue may be mistaken as ovarian tissue
  22. MRI in medium-chain acyl-coenzyme a dehydrogenase deficiency: neuroimaging during the first month
https://doi.org/10.1515/jpem-2017-0099
Keywords for this article
acute lymphoblastic leukemia; growth; obesity; puberty; survivors

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Endocrine aspects in cystic fibrosis
  4. Original Articles
  5. A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis
  6. Cystic-fibrosis related-diabetes (CFRD) is preceded by and associated with growth failure and deteriorating lung function
  7. Partial clinical remission in type 1 diabetes: a comparison of the accuracy of total daily dose of insulin of <0.3 units/kg/day to the gold standard insulin-dose adjusted hemoglobin A1c of ≤9 for the detection of partial clinical remission
  8. Concentrations of leptin, adiponectin and other metabolic parameters in non-obese children with Down syndrome
  9. Parent reported nutritional risk and laboratory indices of cardiometabolic risk and in preschool-aged children
  10. Multinodular goiter in children: treatment controversies
  11. Atopy as a risk factor for subclinical hypothyroidism development in children
  12. Mutation analysis of the NKX2.5 gene in Iranian pediatric patients with congenital hypothyroidism
  13. Health-related quality of life among children with Turner syndrome: controlled cross-sectional study
  14. Growth and pubertal patterns in young survivors of childhood acute lymphoblastic leukemia
  15. Clinical features and genotyping of patients with primary carnitine deficiency identified by newborn screening
  16. Letter to the Editor
  17. Sensitivity and specificity of cystic fibrosis-related diabetes screening methods: which test should be the reference method?
  18. Case Reports
  19. Type 1 rhizomelic chondrodysplasia punctata with a homozygous PEX7 mutation
  20. Severe hypertriglyceridemia at new onset type 1 diabetes mellitus
  21. 45,X/46,XY ovotesticular disorder of sex development revisited: undifferentiated gonadal tissue may be mistaken as ovarian tissue
  22. MRI in medium-chain acyl-coenzyme a dehydrogenase deficiency: neuroimaging during the first month
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 11.11.2025 from https://www.degruyterbrill.com/document/doi/10.1515/jpem-2017-0099/html
Scroll to top button