Long-Term Effects of Treatment for Acute Lymphoblastic Leukemia with and without Cranial Irradiation on Growth and Puberty: A Comparative Study

Hokken-Koelega, Anita C S; Doorn, J W D Van; Hählen, K.; Stijnen, Theo; Keizer-Schrama, S.M.P.F. de Muinck; Drop, S. L. S.

doi:10.1203/00006450-199306000-00008

Cited by 76 publications

(45 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Contrary to some (2,3,10,11,15,18) but not all previous studies (6,14), we found that compared with siblings, patients treated with chemotherapy alone had mildly shorter mean adult heights and a three-fold increased risk of short adult stature across age groups, pubertal status, and secular time periods, even after adjustment for possible demographic confounding variables. Differences in results between this study and others may stem from differences in the definition of "adult/final" heights and in comparison groups.…”

Section: Discussioncontrasting

confidence: 99%

“…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 (2,3,10,11,15,18). However, catch-up growth has not been observed consistently across studies(6,14).…”

Section: Introductionmentioning

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%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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 (...

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…The prolonged survival of children with acute lymphoblastic leukemia (ALL) has changed the focus to the various late effects of the disease and its treatment. Possible serious late effects of ALL and its treatment are second cancers, cardiac dysfunction, renal damage, pulmonary toxicity, hearing loss, dental changes, obesity, hypogonadism, growth retardation, and decreased bone mass [1][2][3][4][5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: Comparison of megadose methylprednisolone and conventional‐dose prednisolone treatments

et al. 2005

View full text Add to dashboard Cite

During recent decades, the survival rate after childhood acute lymphoblastic leukemia (ALL) has improved substantially; consequently, the long-term side effects of ALL and its treatment have gained attention, of which osteoporosis is one of the most important. The purpose of the present study was to compare the influence of different treatment protocols that include high-dose methylprednisolone (HDMP) versus conventional-dose prednisolone (CDP) for remission-induction therapy on bone mineral density (BMD) and serum bone turnover markers in survivors of childhood ALL after cessation of chemotherapy. Thirty-six boy and 23 girl survivors, treated for ALL, were cross-sectionally studied, at a mean age of 11.7 years (range 6-19). Group 1 (n = 30) received CDP therapy (prednisolone, 2 mg/kg/day, orally) and group 2 (n = 29) received HDMP therapy (prednol-L, 900-600 mg/m 2 , orally). All other therapies were similar in both groups. Cranial irradiation was added for high-risk patients as soon as possible after consolidation therapy. We found that mean lumbar spine BMD z score value was -1.75 (0.83) SDS in group 1 and -1.66 (1.21) SDS in group 2. There is no difference between both groups (P = 0.736). The mean BMD z scores of prepubertal and pubertal patients were not significantly different in both groups. Comparison of serum bone turnover parameters of the patients revealed no difference between the two groups. Stepwise regression analysis revealed that lumbar spine BMD z scores was predicted by height SDS and the time past since cessation of therapy, but not age at diagnosis, BMI SDS, cranial radiotherapy, and puberty. Our study results showed that HDMP treatment did not deteriorate the bone mass any more than CDP treatment. These results proved that high-dose steroid therapy over a short period of time in remission-induction treatment would not affect the bone mass any more adversely than would conventional doses approximately 3 years after cessation of chemotherapy. Am.

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

Long-Term Effects of Treatment for Acute Lymphoblastic Leukemia with and without Cranial Irradiation on Growth and Puberty: A Comparative Study

Cited by 76 publications

References 16 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

Bone mineral density and serum bone turnover markers in survivors of childhood acute lymphoblastic leukemia: Comparison of megadose methylprednisolone and conventional‐dose prednisolone treatments

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

Contact Info

Product

Resources

About