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Childhood Leukemia Survivors: Growth Hormone Deficiency, Quality of Life, and Neuropsychological Performance« Back to Volume 23, Issue 2, June 2007 - Table of Contents As a consequence of cranial irradiation, childhood onset, acute lymphoblastic leukemia (ALL) survivors have a significant occurrence of growth hormone deficiency (GHD), often as the only established endocrine sequelae. Previous studies of childhood onset ALL have assessed neuropsychological (NP) functioning in childhood and adolescence, but not in adulthood. Furthermore, NP has not been related to the decline in GH secretion. There is also a lack of information on these patients regarding their self-rated quality of life (QOL) and social functioning. Because of improved survival rate in ALL, these issues have become quite important. Adult patients (n=44) with a median age of 24.8 years, diagnosed at a median age of 4 years, received a target dose of 24 Gy (18-30) and were off chemotherapy for a median of 16.7 years. All subjects had GHD, 91% having a severe deficiency. Four patients received GH treatment in childhood, but not for at least 5 years prior to this study. Appropriate local controls were selected. The level of self-reported QOL, social interaction, and social network was assessed by questionnaires. School education and marital social status were investigated. A battery of NP performance testing was selected with a high sensitivity for subtle brain dysfunction. Results were expressed in mean z-scores for each patient as compared to the control group The patients had significantly lower performances in NP functioning, with a significant negative impact of early age at treatment. No relationship was found between dose cranial radiotherapy (CRT), time since treatment for ALL or gender and the NP functioning. QOL, the social interaction, and social network did not appear to be different from controls, though it is noticeable that significantly more patients were living alone or with their parents. The level of education was significantly lower, but this was not correlated to age at treatment. In the NP functioning tests in 14 of the 20 test variables, the former ALL patients had lower performance (ie, short term memory, spatial ability and speed, peripheral and fine motor speed.) The outcome was poorer in patients with lower age at CRT. A subset of patients treated before the age of 6 years (10/27) had the lowest mean score across all tests. The 14 adult patients with severe GHD who received GH treatment did not exhibit changes that appeared to be different from those observed in the pair matched controls. The GH treatment was monitored in order to maintain plasma insulin-like growth factor (IGF) -I in the middle of the age-adjusted reference range, with a median final GH dose of 0.4 mg/day. The study showed that adult survivors of childhood onset ALL treated with CRT, presenting with severe GHD had significantly impaired NP performance, although self-reported QOL was not affected. Treatment with GH for one year in patients with severe GHD did not induce significant changes. Editor’s CommentPrevious studies on psychosocial sequelae had shown greater negative disturbances in adult survivors of childhood cancer. The authors suggested that their patients may have developed coping strategies adapting to their situation. Surprisingly, the patients did not complain about QOL (using self-rating questionnaires) although their behaviour and social and economic achievements were clearly impaired; nor did they report poorer interpersonal functioning, as reported in another study using interviews. There is a possibility that the patients overestimated their own social interactions, even though marriage was attained in 30% less than would be expected for age. The differences highlight the limitation of such studies, because of differences in testing methods and in choices of control groups. The neurocognitive testing provided more consistent results showing that no further decline in NP capacity occurs in the period from 8 to 27 years after CRT. If this is confirmed by additional studies, it might have a major impact on the management of special education and on expectations for these children. The GH status is another additional issue as GH is per se a risk factor. The one year treatment study was probably too short to induce any significant improvement, although other studies have shown a rapid beneficial effect on attention performance or memory function. It may be possible that earlier and continuous GH treatment would minimize the negative effects on NP performance, allowing better school and professional results. This would also require close follow-up of these childhood cancer patients who are at risk of GHD in order to detect and address the endocrine deficit at its very onset. The effect of GH treatment has to be further evaluated. The risk of secondary tumors in GH treated cancer survivors is discussed in this issue of GGH in “Cancer Survivors, Growth Hormone Treatment, and Second Neoplams”.2 Raphaël Rappaport , MD References - (linked to
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Volume 25 Number 1
June 2009
www.GGHjournal.com
ISSN 1932-9032
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