Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood

Birkebæk, Niels H; Fisker, Sanne; Clausen, Niels; Tuovinen, Veikko; Sindet‐Pedersen, Steen; Christiansen, Jens Sandahl

doi:10.1002/(sici)1096-911x(199806)30:6<351::aid-mpo9>3.0.co;2-d

Cited by 68 publications

(40 citation statements)

References 35 publications

(52 reference statements)

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“…While cranial radiotherapy can affect growth hormone secretion, especially at doses ≥24 Gy (16,21,22), the evidence for growth hormone deficiency following 18 Gy doses has been inconsistent (9,23). The duration of the pubertal growth spurt and peak growth velocity may also be decreased following cranial radiotherapy as a result of growth hormone deficiency (8).…”

Section: Discussionmentioning

confidence: 84%

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Chow

Friedman

Yasui

et al. 2007

The Journal of Pediatrics

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Objectives-To determine risk factors associated with reduced adult height in survivors of childhood acute lymphoblastic leukemia (ALL).Study design-Cross-sectional study. Attained adult height was determined among 2,434 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of five-year survivors of common pediatric cancers diagnosed from [1970][1971][1972][1973][1974][1975][1976][1977][1978][1979][1980][1981][1982][1983][1984][1985][1986], and compared with 3,009 siblings.Results-All survivor treatment exposure groups (chemotherapy alone, chemotherapy with cranial or craniospinal radiotherapy) had decreased adult heights and an increased risk of adult short stature (height standard deviation score < −2) compared with siblings (p<0.001). Compared with siblings, the risk of short stature for survivors treated with chemotherapy alone was elevated (OR 3.4, 95% CI 1.9, 6.0). Among survivors, significant risk factors for short stature included diagnosis of ALL prior to puberty, higher dose cranial radiotherapy (≥20 Gy versus <20 Gy), any radiotherapy to the spine, and female sex.Conclusions-Survivors of childhood ALL are at increased risk of adult short stature, including those treated with chemotherapy alone. Risk is highest for those treated with cranial and craniospinal radiotherapy at a young age. PO Box 19024, Seattle, WA 98109-1024. Phone (206) 667-7724, Fax (206) 667-5948, email: ericchow@u.washington.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The authors disclose no potential conflicts of interest. Cranial and craniospinal radiotherapy were commonly used in the 1970s and early 1980s to treat as well as to prevent the spread of acute lymphoblastic leukemia (ALL) to the central nervous system (CNS) in children. While radiotherapy was effective, it was associated with adverse endocrine and neurocognitive outcomes(1). As a result, over the past three decades, radiotherapy doses have been reduced or eliminated in an attempt to decrease these adverse long-term outcomes, and have been replaced by more intensive chemotherapy.Several studies have examined growth in ALL survivors. Growth deficits have been reported consistently following doses of ≥24 Gy cranial radiotherapy, but the data are less consistent for doses <20 Gy(2-17). The effect on loss of stature was greater in children who also received radiotherapy to the spine, secondary to direct inhibition of vertebral growth(13). For most studies in which the impact of chemotherapy without radiotherapy was examined, growth suppression during treatment was followed by catch-up growth (...

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Section: Discussionmentioning

confidence: 84%

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Chow

Friedman

Yasui

et al. 2007

The Journal of Pediatrics

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“…[327][328][329][330] Elevated leptin concentrations and leptin receptor abnormalities have been reported in childhood cancer survivors. 331,332 Radiation exposure to the hypothalamic-pituitary axis in childhood can result in late-onset deficiency of GH secretion and subsequent development of obesity in adulthood. 318,321,[333][334][335][336] GH helps determine fat cell size, fat cell differentiation, 334 and concentrations of resistin, 333 all of which are important determinants of insulin sensitivity.…”

Section: Pathophysiology Of Obesity In Childhood Cancer Survivorsmentioning

confidence: 99%

“…318,321,[333][334][335][336] GH helps determine fat cell size, fat cell differentiation, 334 and concentrations of resistin, 333 all of which are important determinants of insulin sensitivity. 332 Impaired GH concentrations in survivors potentially affect the development of obesity, insulin resistance, and type 2 diabetes mellitus. [334][335][336][337] In a study of young adult ALL survivors, cranial radiation was a risk factor for elevated total, abdominal, and visceral adiposity; reduced lean body mass; a higher risk of metabolic syndrome; and altered insulin-like growth factor-1 and leptin concentrations.…”

Section: Pathophysiology Of Obesity In Childhood Cancer Survivorsmentioning

confidence: 99%

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

Lipshultz¹,

Adams²,

Colan³

et al. 2013

Circulation

492

436

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“…The rise in serum leptin levels at 6 months after diagnosis could be secondary to the rise in body fat (as indicated by the increase in skinfolds) and the use of corticosteroids, which stimulate leptin synthesis (33). We found no differences in serum leptin levels between girls and boys or between irradiated and non-irradiated patients, whereas in Birkebaek's study, serum leptin was signi®cantly higher in patients treated with cranial irradiation compared with the non-irradiated group (34).…”

Section: Timementioning

confidence: 99%

Anthropometric parameters and their relationship to serum growth hormone-binding protein and leptin levels in children with acute lymphoblastic leukemia: a prospective study

Arguelles¹,

Barrios²,

Buño³

et al. 2000

European Journal of Endocrinology

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Objective: The aim of this study was to follow auxological parameters and their relationship to serum growth hormone-binding protein (GHBP) and leptin levels in children with acute lymphoblastic leukemia (ALL). Design and methods: In total, 26 prepubertal children with ALL were studied. We report these data at the time of the clinical diagnosis (n 26) and at 6 (n 21), 12 (n 21), 18 (n 21), 24 (n 20), 30 (n 16) and 36 months (n 16) after beginning treatment. Results: Serum GHBP levels decreased during the ®rst 18 months and returned to normal when therapy was withdrawn. Height SDS increased at 24 months after diagnosis. Weight and the upper arm circumference had increased 6 months after chemotherapy withdrawal, whereas tricipital and subscapular skinfolds had increased both at 6 months after diagnosis and 6 months after therapy had stopped. Therefore, the tendency to become overweight is both an early and a late side-effect of anti-leukemia therapy. A signi®cant positive correlation was found between serum leptin levels and every nutritional anthropometric parameter, with body mass index having the best relationship. However, serum GHBP levels were only correlated with BMI at the end of the study. No correlation was found between leptin and GHBP. Conclusions: In children with ALL, linear growth is compromised during the acute phase of their illness and therapy; this is probably secondary to a state of partial and transient GH insensitivity. These patients tend to become obese after therapy withdrawal, with leptin being an excellent nutritional marker.

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Growth and endocrinological disorders up to 21 years after treatment for acute lymphoblastic leukemia in childhood

Cited by 68 publications

References 35 publications

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Decreased Adult Height in Survivors of Childhood Acute Lymphoblastic Leukemia: A Report from the Childhood Cancer Survivor Study

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

Anthropometric parameters and their relationship to serum growth hormone-binding protein and leptin levels in children with acute lymphoblastic leukemia: a prospective study

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