Date Published: May 31, 2019
Publisher: Public Library of Science
Author(s): Kayla L. Foster, Kathleen D. Kern, Tiffany M. Chambers, Philip J. Lupo, Kala Y. Kamdar, Michael E. Scheurer, Austin L. Brown, Roland A Ammann.
As survival rates for childhood acute lymphoblastic leukemia (ALL) continue to improve, there is growing concern over the chronic health conditions that survivors face. Given that survivors of childhood ALL are at increased risk of cardiovascular complications and obesity, we sought to characterize BMI trends from diagnosis through early survivorship in a multi-ethnic, contemporary cohort of childhood ALL patients and determine if early weight change was predictive of long-term weight status.
The study population consisted of ALL patients aged 2–15 years at diagnosis who were treated with chemotherapy alone at Texas Children’s Hospital. Each patient had BMI z-scores collected at diagnosis, 30-days post-diagnosis, and annually for five years. Linear regression models were estimated to evaluate the association between: 1) BMI z-score change in the first 30 days and BMI z-scores at five-years post-diagnosis; and 2) BMI z-score change in the first year post-diagnosis and BMI z-scores at five-years post-diagnosis.
This retrospective cohort study included longitudinal data from 121 eligible patients. The mean BMI z-scores for the population increased significantly (p-value<0.001) from baseline (mean = 0.25) to 30 days post-diagnosis (mean = 1.17) before plateauing after one year post-diagnosis (mean = 0.99). Baseline BMI z-scores were statistically significant predictors to five year BMI z-scores (p <0.001). Independent of baseline BMI z-score and other clinical factors, the BMI z-score at one year post-diagnosis was significantly associated with BMI z-score at five-years post-diagnosis (β = 0.63, p <0.001), while BMI z-score at 30 days post-diagnosis was not (β = 0.10, p = 0.23). Our results suggest that weight gain within the first year after diagnosis is more strongly associated with long-term BMI than early weight gain (within 30 days). If confirmed, this information may help identify a window of time during therapy when ALL patients would benefit most from weight management directed interventions.
Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with more than 5,000 cases diagnosed annually in the United States . With the emergence of more effective chemotherapeutic protocols, ALL is curable in more than 90% of cases . As survival has increased, research focus has shifted to long-term health outcomes of ALL survivors. Unfortunately, curative therapy is associated with a burden of chronic health conditions among survivors, with 95.5% of child and adolescent cancer survivors experiencing at least one chronic disease by 45 years of age [3, 4]. Compared to age-matched peers, ALL survivors have a four-fold increased risk of mortality secondary to cardiovascular events . Because obesity plays a major role in cardiovascular health, approaches that minimize treatment-related weight gain may improve the overall health of childhood ALL patients and survivors [6–8].
In this retrospective cohort study, subjects were those diagnosed with ALL at Texas Children’s Hospital between 2005 and 2012. To reduce heterogeneity in treatment exposures, patients were excluded if they relapsed, received bone marrow transplant, or were exposed to cranial or craniospinal irradiation therapy (CRT). In addition, patients with conditions that might impact growth trajectories (e.g., Down syndrome, dwarfism) were also excluded. Finally, the study analysis was restricted to patients two to 15 years of age at diagnosis, thereby permitting the calculation of BMI z-scores for each individual at each study visit. This study was approved by the Baylor College of Medicine Institutional Review Board (IRB).
We identified a total of 121 eligible patients diagnosed with B-cell ALL and treated at Texas Children’s Hospital between 2005 and 2012 (Fig 1). The study population was 51% male (n = 62), 56% diagnosed before the age of five (n = 68), and comprised of 58% Hispanic (n = 70) and 36% non-Hispanic white (n = 44) patients (Table 1). Most patients were treated on or according to AALL0331 (64%). The distribution of demographic factors was similar between patients excluded from the analysis due to missing or incomplete data and patients included in the analysis (results not shown): age (p-value = 0.33), race/ethnicity (p-value = 0.97), and gender (p-value = 0.75).
This longitudinal study of a contemporary multi-ethnic cohort of childhood ALL patients demonstrates that increases in weight are common during therapy and persist into survivorship. This finding adds to the growing body of evidence that weight gain is a common consequence of modern pediatric ALL chemotherapy, even among patients spared CRT [14–17]. Few, if any, assessments of obesity in childhood ALL patients have evaluated weight change during treatment windows that predict post-treatment adiposity. Specifically, although change in BMI z-scores was most pronounced during the first 30 days of therapy, BMI z-score at 30 days was not a statistically significant predictor of BMI z-scores at five years post-diagnosis after accounting for clinical and demographic factors. Weight often peaked after 30 days, but did not return to pre-treatment levels. Importantly, weight maintained at one year post-diagnosis did correlate with weight maintained at five years post-diagnosis. This observation has potential clinical implications for monitoring and intervening on weight gain during childhood ALL therapy.