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Height in Survivors of Childhood Acute Lymphoblastic Leukemia« Back to Volume 23, Issue 3, November 2007 - Table of Contents This paper describes adult height in a Childhood Cancer Survivor Study (CCSS) cohort of 2434 subjects who were at least 5-year survivors of acute lymphoblastic leukemia (ALL) and were diagnosed between 1970 and 1986. Their data were compared to that of 3009 siblings selected for being the closest in age to the proband. Only those over 18 years of age were included. Survivors were excluded from this analysis if they were diagnosed after 17 years of age or if they had a recurrence of their primary leukemia, a secondary malignant neoplasm, or underwent stem-cell transplant before 18 years of age. Cumulative chemotherapy doses were categorized into none, low, medium, or high based on tertiles from previously published end-cut points. For some of the agents dosage information was not available and exposure was recorded as yes or no. Central nervous system (CNS) radiotherapy doses were abstracted in 5-Gy increments. Of the survivors who received cranial radiotherapy, 95% were treated with doses of 15 to 29 Gy and as a result, radiotherapy was characterized into <20 Gy and >20 Gy. Height was expressed in absolute terms as well as SDS. Pubertal status was not always recorded, therefore this variable was dichotomized at age 8 for girls and 10 for boys. The median age of the study cohort was 27 years, and 51% were female. Median age of the siblings was 31 and 52.7% were female. All survivor treatment groups, including those treated with chemotherapy alone, had decreased adult height and height SDS compared with siblings (p<0.001). Effects of radiotherapy on adult height SDS differed between those who were prepubertal versus postpubertal at diagnosis. The height SDS was decreased at all doses of cranial and craniospinal radiotherapy in survivors diagnosed before puberty, compared with those treated with chemotherapy alone. Those survivors who had received >20 Gy of cranial radiotherapy were on average shorter with height SDS scores on average 0.88 lower than those treated with cranial radiotherapy alone. Among survivors diagnosed after pubertal onset, significant negative impact on height SDS was not seen on any cranial radiotherapy dose as compared with chemotherapy alone. On average the adult height SDS of survivors treated after pubertal onset remained shorter than their siblings. All survivor exposure groups were at significant greater risk of adult short stature (that is height SDS < −2) as compared with siblings. No chemotherapeutic agent analyzed had a consistent dose effect on adult height SDS analyzed individually or in combination. There was an increased proportion of female survivors with adult short stature (12.5%) as compared with male survivors (5.5%). The authors stated that this report represents the largest cohort of adult ALL survivors evaluated for adult height to date. Significant differences in height outcomes between survivors treated with high doses of cranial radiotherapy as well as those treated with lower dose cranial radiotherapy versus chemotherapy alone were demonstrated. Survivors who received any spinal radiotherapy had the shortest adult heights. Mechanisms by which cranial radiotherapy affects short stature remain uncertain. It is speculated that at higher doses of radiation there may have been some degree of growth hormone deficiency especially as it relates to the pubertal growth spurt and peak growth velocity. The second possibility is that cranial radiotherapy exerts its effects on pubertal timing. It would appear that early puberty occurs, especially in females, when treated at an early age. A combination of growth hormone insufficiency and early puberty is certainly associated with short adult stature. Findings in the current study are consistent with this hypothesis since the risk of adult short stature was greater in those diagnosed at a younger age, and girls were more affected than boys. The authors pointed out that the limitations of the study included the use of self or proxy reported height data, lack of longitudinal growth information, and the specific time of documentation of pubertal status. However, the large size of the study and the use of sibling controls helped to validate the significance of the differences found. Finally, the authors stated that most patients with ALL were currently treated with chemotherapy alone. Therefore the relationship between chemotherapy agents and linear growth velocity should be available in the future. Chow E, Friedman D, Yasui Y, et al. Decreased adult height in survivors of childhood acute lymphoblastic leukemia (ALL): A report from the Childhood Cancer Survivor Study. J Pediatr. 2007:150:370-5. Editor’s CommentThis paper is accompanied by a thoughtful editorial by Oberfield.1 Her comments included a discussion of previous reports from the CCSS regarding morbidity among childhood cancer survivors and specifically those who were survivors of childhood brain cancers and were subsequently treated with growth hormone. Oberfield points out shortcomings with regard to self reported or proxy reported height and the definition of prepubertal and pubertal based on age, but affirms the uniqueness of the study because of its large size and the fact that even with chemotherapy alone there was a greater than threefold increased risk of decreased stature. The data in this study involved survivors of ALL who were treated with a treatment regimen which differs from that currently in use. It clearly demonstrated that previous treatment regimens were associated with reduced adult height. It is hoped that oncologists will continue to carefully record auxologic and pubertal data on their patients so that similar long-term outcomes can be examined from a different therapeutic era in the future. William L. Clarke, MD Reference - (linked to
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Volume 24 Number 1
May 2008
www.GGHjournal.com
ISSN 1932-9032
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