ALL is the most common childhood malignancy.1
With current chemotherapy regimens, prolonged survival is anticipated in approximately 80% of patients.3
However, treatment of ALL has a number of long-term sequels including obesity, the metabolic syndrome, secondary malignancies, cardiotoxicity, growth and puberty disorders, and educational and psychological dysfunction. Our results indicate an increased frequency of metabolic syndrome in long-term survivors of childhood ALL. Obesity was observed in one forth of children and adolescents previously treated for ALL. Nearly 3/4 of obese patients had metabolic syndrome. The metabolic syndrome was present very early after completion of ALL therapy.
The prevalence of both the metabolic syndrome and its components may influence by differences in genetic background, dietary habits, levels of physical activity, population age and sex structure and levels of over and under-nutrition.16
In the developing countries, the overall prevalence of the metabolic syndrome in healthy children and adolescents based on modified ATP III criteria ranges between 2.2-14.1%.17–20
The prevalence of metabolic syndrome was higher in overweight and obese children in this study as was reported by Goodman and crutz.12,21
In Kourti et al study the metabolic syndrome prevalence in young ALL survivors was 5.76%.22
This rate is much lower than the overall metabolic syndrome prevalence of Trimis et al16
patients (11%). However, Trimis et al found that this rate was higher in patients who received combination of chemotherapy and cranial irradiation (22%) versus chemotherapy alone (8%).6
In contrast, in our study the overall prevalence of metabolic syndrome was found quite high (20%). Whether differences in genetic predisposition or mode of treatment can explain this needs further investigation. Likewise, in our study the prevalence of metabolic syndrome was higher in patients who received combination of chemotherapy and cranial irradiation versus chemotherapy alone.
Obesity is a well known adverse consequence of ALL and an unusually high proportion of survivors are overweight and obese.6,22
Children treated for ALL gain weight from the time of diagnosis and it continues well beyond the end of treatment.23
A number of risk factors predisposed the patients to excess weight gain, including a low BMI standard deviation score at diagnosis, younger age at diagnosis, gender, cranial radiotherapy and reduced total energy expenditure secondary to reduced habitual physical activity.22–24
Our results are in accordance with other studies that documented an increased prevalence of obesity in the initial years of follow-up among survivors of child-hood ALL.
It was shown that GH deficiency was strongly associated with cranial radiation treatment in young ALL survivors who presented with an abnormal pattern of serum lipids and obesity.6,25
Abnormally low GH was also associated with higher fasting insulin, and higher HOMA index.26
In our study, nearly one forth of children who received cranial radiotherapy developed metabolic syndrome. One of the limitations of this study is the lack of control group. In addition, we did not measure the GH level.
In Talvensaari study,13
a higher fasting plasma insulin level was seen in survivors of child-hood cancer than compared to a control group. In the present study, fasting plasma insulin level was significantly higher in children with metabolic syndrome than those without. Hyperinsulinemia in the survivors of ALL may be partly due to obesity and partially secondary to hepatotoxic effect of chemotherapy. Synthesis of insulin-like growth factor binding protein-1(IGFBP-1) and sex hormone binding globulin (SHBG) in the liver has been shown to be regulated by insulin and hyperinsulinemia is associated with reduced levels of these proteins after chemotherapy.27,28
Obesity is a strong independent risk factor for insulin resistance.13
In our study, insulin resistance was detected in nearly 3/4 of survivors with metabolic syndrome and all of them were obese.
In conclusion, metabolic syndrome in survivors of childhood leukemia in Iran is not uncommon. Nearly all of the obese patients had metabolic syndrome. Early identification of metabolic syndrome among survivors of childhood leukemia can reduce the risk of cardiovascular morbidity and mortality. Weight control and regular physical exercise should be emphasized in their follow-up.