Growth in Children Treated for Acute Lymphoblastic Leukaemia

Shalet, SM; Clayton, Peter E.; Morris‐Jones, P. H.; Price, David A.

doi:10.1016/s0140-6736(88)91246-9

Cited by 157 publications

(103 citation statements)

References 6 publications

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“…Those who received any form of spinal radiotherapy had the shortest adult heights among all survivor groups. Prior studies had not been consistent in finding differences in final height between survivors treated with 18 Gy versus 24 Gy cranial radiotherapy (3)(4)(5)7,12,(15)(16)(17), or between 18 Gy and treatment with chemotherapy alone (3,6,14). These studies had relatively few subjects who reached adult height (N <200), limiting their statistical power to detect differences.…”

Section: Discussionmentioning

confidence: 99%

“…Growth deficits have been reported consistently following doses of ≥24 Gy cranial radiotherapy, but the data are less consistent for doses <20 Gy (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(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).…”

Section: Introductionmentioning

confidence: 99%

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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: 99%

Section: Introductionmentioning

confidence: 99%

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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“…The assessor of the HSC records (AL) felt that the system provided inadequate means with which to record growth hormone deficiency. Many patients with ALL experience a temporary reduction in growth velocity (Griffin & Wadsworth, 1980;Clayton et al, 1988) while some suffer frank growth hormone deficiency. The multi-attribute system has no mechanism with which to record directly the endocrine morbidity.…”

Section: Discussionmentioning

confidence: 99%

The comprehensive assessment of health status in survivors of childhood cancer: application to high-risk acute lymphoblastic leukaemia

Feeny

Leiper²,

Barr³

et al. 1993

Br J Cancer

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Summary The health status of 69 survivors of high-risk acute lymphoblastic leukaemia (ALL) is assessed using a multi-attribute classification system. Seven attributes are included: sensation, mobility, emotion, cognition, self-care, pain and fertility. Three to five levels of functioning are defined for each attribute. Comprehensive health states are described as a specific combination of seven attribute levels. The system captures combinations of sequelae. The system provides a compact but comprehensive tool for long term follow up of survivors of childhood cancer. The results underscore the cognitive and emotional burdens of morbidity affecting survivors of high-risk ALL.

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“…There have been many reports of poor growth in children with acute lymphoblastic leukemia (ALL), especially during periods of intensive chemotherapy, but growth may return to normal during less-intensive periods and may show evidence of further catch-up after completion of chemotherapy (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Of greater concern are a number of retrospective crosssectional studies on survivors of ALL that describe reduced bone mineral density (BMD) at various sites (14 -16).…”

mentioning

confidence: 99%

Bone Turnover and Growth During and After Continuing Chemotherapy in Children with Acute Lymphoblastic Leukemia

et al. 2000

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Children treated for acute lymphoblastic leukemia may develop reduced bone mineral density during treatment, but there is little information on the mechanisms involved. In a prospective, longitudinal study on 15 children with ALL, we undertook serial measurements of markers of bone and collagen turnover, insulinlike growth factor (IGF)-I and its binding proteins (IGFBPs)-3 and -2 during the second year of continuing chemotherapy. In eight patients we also measured lower leg length by knemometry. Height SD scores, lower leg length velocity, IGF-I, and markers of bone collagen turnover did not differ significantly from healthy children. However, bone alkaline phosphatase, a marker of the differentiated osteoblast, was lower (mean SD score, Ϫ0.64; p Ͻ 0.0001), whereas procollagen type III N-terminal propeptide (P3NP, a marker of soft tissue collagen turnover; mean SD score, ϩ0.93, p Ͻ 0.05), IGFBP-3 (mean SD score, ϩ0.76; p Ͻ 0.01), and IGFBP-2 (mean SD score, ϩ1.24, p ϭ 0.01) were all higher than in healthy children. IGFBP-3 decreased during episodes of afebrile neutropenia (p Ͻ 0.05). Within 3 mo after completion of treatment, bone ALP increased in all eight patients, but collagen markers showed little change. IGFBP-2 returned to normal posttreatment, but P3NP and IG-FBP-3 remained significantly elevated compared with healthy children (mean SD scores, ϩ1.51 and ϩ1.36, respectively; p Ͻ 0.01). We conclude that continuing chemotherapy was associated with normal growth and bone collagen turnover but enhanced soft tissue collagen turnover. Bone bone alkaline phosphatase was low throughout treatment, which suggests impaired osteoblast differentiation resulting from a direct effect of chemotherapy on bone. Although the effect was reversible, the long-term implications for bone health in survivors remain uncertain. There have been many reports of poor growth in children with acute lymphoblastic leukemia (ALL), especially during periods of intensive chemotherapy, but growth may return to normal during less-intensive periods and may show evidence of further catch-up after completion of chemotherapy (1-13). Of greater concern are a number of retrospective crosssectional studies on survivors of ALL that describe reduced bone mineral density (BMD) at various sites (14 -16). This may be associated with increased fracture risk, reduced peak bone mass, and a theoretical risk of osteoporosis in adult life. However, these previous studies reflect the outcome of earlier treatment protocols, most of which included cranial irradiation and are now obsolete. Current protocols generally use more intensive chemotherapy regimens but avoid cranial irradiation in all but a few high-risk cases. Recently, a number of prospective longitudinal studies have reported that the prevalence of radiologic osteopenia and fracture in children with ALL increases and that BMD decreases during chemotherapy, in the absence of cranial irradiation (17)(18)(19). However, the mechanisms responsible for these observations remain to be elucidated.There are a num...

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Growth in Children Treated for Acute Lymphoblastic Leukaemia

Cited by 157 publications

References 6 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

The comprehensive assessment of health status in survivors of childhood cancer: application to high-risk acute lymphoblastic leukaemia

Bone Turnover and Growth During and After Continuing Chemotherapy in Children with Acute Lymphoblastic Leukemia

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