Screening Survivors of Childhood Acute Lymphoblastic Leukemia for Obesity, Metabolic Syndrome, and Insulin Resistance

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Abstract

Acute lymphoblastic leukemia (ALL) survivors were screened for risk factors of cardiovascular disease. Forty-four ALL survivors in first remission were enrolled. Twenty-six also received 12-18 Gy cranial radiotherapy (RT). Patients' body mass indexes (BMIs) at dignosis and during the study were compared. Metabolic syndrome (MS) evaluation was performed in patients, parents, and siblings older than 6 years. Homeostasis Model Assessment (HOMA) index of the survivors was also calculated. In survivors with impaired fasting glucose levels, oral glucose tolerance test (OGTT) was performed. Thyroid functions and IGF-1 and/or IGFBP-3 levels of the survivors who received cranial RT were evaluated. Median age of the survivors was 11.5 years (6-23). At diagnosis, mean BMI percentile was 46.7 (3-95) and mean z-score was -0.09 ± 1.14; during the study, these values rose to 71.1 ± 25.6 (3-100) and 0.8 ± 0.94, respectively (P < .001). One patient (2.2%) and nine survivors (20%) were obese at diagnosis and during the study, respectively (P = .005). Survivors had significantly higher BMI percentile and BMI z-score compared to their siblings (P = .006 and P = .011, respectively). The study group was small and we could not show a correlation of the patients' obesity with RT, thyroid functions, IGF-1, and IGFBP-3 levels. In three survivors (6.8%), there was MS. Maternal and paternal MS was not found as a risk factor for MS of the survivors (P = .1, P = .5, respectively). The HOMA index revealed insulin resistance (IR) in 12 (27.2%) of the survivors, whereas OGTT revealed abnormal glucose regulation and/or IR in four. As a conclusion, ALL survivors have high risk for obesity and MS.

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Obesity in adult survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

Annelien Mertens, Terry Vik, P D Inskip … (2003)

To determine whether adult survivors (>or= 18 years of age) of childhood acute lymphoblastic leukemia (ALL) are at increased risk for obesity and to assess patient and treatment variables that influence risk. A retrospective cohort of participants of the Childhood Cancer Survivor Study was used to compare 1,765 adult survivors of childhood ALL to 2,565 adult siblings of childhood cancer survivors. Body-mass index (BMI; kilograms per square meter), calculated from self-reported heights and weights, was used to determine the prevalence of being overweight (BMI, 25-29.9) or obese (BMI >or= 30.0). Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for being overweight or obese among ALL survivors relative to the sibling control group. The age- and race-adjusted OR for being obese in survivors treated with cranial radiation doses >or= 20 Gy in comparison with siblings was 2.59 for females (95% CI, 1.88 to 3.55; P or= 20 Gy (OR, 3.81; 95% CI, 2.34 to 5.99; P or= 20 Gy is associated with an increased prevalence of obesity, especially in females treated at a young age. It is imperative that healthcare professionals recognize this risk and develop strategies to enhance weight control and encourage longitudinal follow-up.

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Insulin resistance syndrome in children.

Noel Maclaren, Vadim S. Ten (2004)

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.

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Twenty-five-year follow-up among survivors of childhood acute lymphoblastic leukemia: a report from the Childhood Cancer Survivor Study.

S. Li, Yutaka Yasui, Rajen Mody … (2008)

Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late effects of cancer therapy. Five-year ALL survivors (< 21 years at diagnosis; n = 5760 eligible, 4151 participants), diagnosed from 1970 to 1986 were compared with the general population and a sibling cohort (n = 3899). Cumulative mortality of 5760 5-year survivors was 13% at 25 years from diagnosis. Recurrent ALL (n = 483) and second neoplasms (SNs; n = 89) were the major causes of death. Among 185 survivors, 199 SNs occurred, 53% in the CNS. Survivors reported more multiple chronic medical conditions (CMCs; odds ratio [OR], 2.8; 95% CI, 2.4-3.2) and severe or life-threatening CMCs (OR, 3.6; 95% CI, 3.0-4.5) than siblings. Cumulative incidence of severe CMCs, including death, 25 years from diagnosis was 21.3% (95% CI, 18.2-24.4; 23.3% [95% CI, 19.4-27.2] and 13.4% [95% CI, 8.4-18.4] for irradiated and nonirradiated survivors, respectively). Survivors reported more adverse general and mental health, functional impairment, and activity limitations compared with siblings (P < .001). Rates of marriage, college graduation, employment, and health insurance were all lower compared with sibling controls (P < .001). Long-term survivors of childhood ALL exhibit excess mortality and morbidity. Survivors who received radiation therapy as part of their treatment or had a leukemia relapse are at greatest risk for adverse outcomes.