Abstract 2185: Childhood obesity is associated with persistent minimal residual disease (MRD) following induction therapy for pediatric acute lymphoblastic leukemia
Authors: Orgel Etan , Tucci Jonathan , Alhushki Wassem , Freyer David R. , Abdel-Azim Hisham , Mittelman Steven D. 
Published: May 2015

Abstract
Background: The epidemic of childhood obesity poses substantial treatment challenges for the care of children with acute lymphoblastic leukemia (ALL). Obesity at time of diagnosis of ALL is associated with worse survival as well as treatment-related morbidity. Inability to achieve a deep initial remission following Induction as evidenced by persistent MRD in the bone marrow is associated with poor survival and has thus become the predominant modern prognostic indicator. We therefore hypothesized that obesity at time of diagnosis of ALL is associated with MRD positivity at the end-of-Induction disease evaluation.
Methods: In a cohort of children 1 - 20 years old treated for B-precursor ALL (BP-ALL) at our institution from 2008 to 2013 on Children's Oncology Group (COG) treatment regimens, we examined MRD at end-of-Induction as determined by multidimensional flow cytometry. A threshold of 0.01% was used to determine MRD positive versus negative as per COG regimens. Overweight and obese categories were defined as 85-95th and ≥95th percentile for body mass index (BMI) according to the CDC population norms. Logistic regression analyses were performed controlling for age, gender, ethnicity/race, presence/absence of Down Syndrome (due to the high prevalence of obesity), National Cancer Institute (NCI) risk category, cytogenetic classification (standard, favorable, unfavorable, unknown), and CNS status at diagnosis. BMI was evaluated as both a continuous variable and also as per normal, overweight, obese categories.
Results: We identified 198 patients with BP-ALL and evaluable MRD, 119 with NCI SR-ALL and 79 with NCI HR-ALL. Of these, 55 (27.8%) had positive MRD at end-of-Induction [27 SR-ALL (22.7%), 28 HR-ALL (35.4%). In the obese group, 45.2% (19/42) were MRD+, compared to only 22.8% (29/127) of normal weight and 24.1% (7/29) of overweight patients. After controlling for above covariates, obese patients had a statistically significantly increased risk for MRD positivity at end-of-Induction [Odds Ratio (OR) 2.64, 95 percent Confidence Interval (95%CI) 1.13-6.19, p=0.025]. Similarly, each percentile increase in BMI significantly corresponded to an increased risk for MRD positivity (OR 1.08, 95%CI 1.00-1.17, p=0.046).
Conclusion: Obese children at diagnosis of BP-ALL are at significantly increased risk for persistent MRD in the bone marrow at end-of-Induction. With the established strong adverse association of persistent MRD with poorer survival, this implies that obesity adversely influences survival as early as this initial phase of treatment. Our results support the need for further research into mechanisms underlying this phenomenon and potential up-front strategies to improve efficiency of remission induction in this population.
Citation Format: Etan Orgel, Jonathan Tucci, Wassem Alhushki, David R. Freyer, Hisham Abdel-Azim, Steven D. Mittelman. Childhood obesity is associated with persistent minimal residual disease (MRD) following induction therapy for pediatric acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2185. doi:10.1158/1538-7445.AM2014-2185