BMI alterations during treatment of childhood ALL—response

To the Editor: We appreciate the data shared by Tragiannidis et al. from their experience with a cohort of patients treated per ALL BFM-95 in Northern Greece. It is very interesting that despite having a much leaner baseline population ( 0.4 median baseline BMI z-score vs. 0.64 in our cohort), their ALL patients also demonstrated increased weight gain over the course of therapy [1]. They report a similar initial increase in BMI z-score; however, this decreased as the patients progressed further into therapy. While it is reported that the median z-scores decreased at 12 and 24 months post-diagnosis, more detail regarding the actual values and statistical methodology may help understand these trends. However, from these data as well as other published data, the trajectory of BMI change during ALL therapy does differ to some degree across populations, for which there are likely treatment, host and environment-related risk factors. While we agree with Tragiannidis et al. that the obesity or an overweight state is reversible for some patients post-chemotherapy, there are extensive data that shows obesity persists for many, extending into the long-term survivorship period and increasing risk for longterm cardiac and metabolic complications [2]. In our study, the use of corticosteroids during maintenance therapy is one of a number of potential etiological risk factors for worsened obesity, recognizing that there are likely psychological factors that motivate parents to restrict physical activity, including concern for injury or illness. We propose that a family-based diet and exercise intervention may mitigate excessive weight gain and address physiologic and psychosocial risk factors for obesity. As the literature has shown, cranial radiation at 18–24 Gy is an important predisposing factor to obesity in long-term survivors [2,3]. However, this may not be true of patients on active therapy; in our cohort, all patients received <24 Gy of cranial radiation therapy, and radiation was actually associated with decreased BMI [1]. There is emerging evidence that patient’s with ALL are also at increased risk for other components of the metabolic syndrome (hypertension, dyslipidemia, and insulin resistance), and we plan to continue to work to further delineate this association [4,5]. There is some evidence that polymorphisms in the leptin receptor are associated with obesity in females who received cranial radiation, and additional research in this area may permit more targeted interventions in those at highest risk [6].