Obesity and survival in a cohort of predominantly Hispanic children with acute lymphoblastic leukemia

University of Texas at San Antonio, San Antonio, Texas, United States
Journal of Pediatric Hematology/Oncology (Impact Factor: 0.96). 10/2006; 28(9):575-8. DOI: 10.1097/01.mph.0000212985.33941.d8
Source: PubMed

ABSTRACT Acute lymphoblastic leukemia (ALL), the most common malignancy in children, constitutes 25% of all pediatric cancer. Childhood cancer patients who are obese at diagnosis represent a particular challenge for the oncologist. Obesity may complicate chemotherapy dose determination, and has been associated with decreased overall and event-free survival in a number of adult cancer patients, and more recently in pediatric patients. The purpose of the present study was to examine whether obesity at diagnosis was associated with decreased overall and event-free survival in a cohort of 322 predominantly Hispanic pediatric patients with B-precursor ALL. Obesity was classified as an age-standardized and sex-standardized body mass index z-score at or above the 95th percentile. Hazard ratios (HRs) for overall and event-free survival were assessed using Cox proportional hazards regression modeling. Obesity at diagnosis was not associated with decreased overall survival (HR = 1.40, 95% confidence interval = 0.69-2.87) or event-free survival (HR = 1.08, 95% confidence interval = 0.65-1.82) in the overall cohort or in either of the 2 age-at-diagnosis (2 to 9 y; 10 to 18 y) subgroups. Our finding of no obesity-related prognostic effect in the overall cohort and in the under 2 to 9-year age-at-diagnosis cohort was consistent with the previous large-scale study of ALL patients; the absence of a prognostic effect in the 10 to 18-year age-at-diagnosis cohort, however, conflicted with previous findings.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is associated with poorer event-free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). Persistent minimal residual disease (MRD) in the bone marrow as measured by multidimensional flow cytometry (MDF) is a key early prognostic indicator and is strongly associated with EFS. We therefore hypothesized that obesity during induction would be associated with positive end of induction MRD (≥0.01%). We analyzed MDF of end-induction bone marrow samples from a historical cohort of 198 children newly diagnosed with B-precursor ALL (BP-ALL) and treated with Children's Oncology Group induction regimens. We assessed the influence of body mass index (BMI) on risk for positive end-induction MRD in the bone marrow. In our cohort of BP-ALL, 30 children were overweight (15.2%) and 41 obese (20.7%) at diagnosis. Independent of established predictors of treatment response, obesity during induction was associated with significantly greater risk for persistent MRD (Odds Ratio 2.57, 95% Confidence Interval 1.19-5.54, p=0.016). Obesity and overweight were associated with poorer EFS irrespective of end-induction MRD (p=0.012). Obese children with newly diagnosed BP-ALL are at increased risk for positive end-induction MRD and poorer EFS.
    Blood 10/2014; 124(26). DOI:10.1182/blood-2014-08-595389 · 9.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies regarding the influence of weight on event-free survival (EFS) and treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL) considered only weight at diagnosis. Inasmuch as weight varies substantially over treatment, we hypothesized its impact on EFS is instead determined by cumulative time spent at an extreme weight during therapy and on TRT by weight at the time of toxicity. In a cohort of 2,008 children treated for high-risk ALL in Children's Oncology Group study CCG-1961, we determined the effect on EFS of cumulative time receiving therapy at an extreme weight (either obese or underweight) between end of induction and start of maintenance therapy. We also evaluated the association between weight category and incidence and patterns of TRT during 13,946 treatment courses. Being obese or underweight at diagnosis and for ≥ 50% of the time between end of induction and start of maintenance therapy resulted in inferior EFS (hazard ratios, 1.43 and 2.30, respectively; global P < .001). Normalization of weight during that period resulted in mitigation of this risk comparable to never being obese or underweight. Obese or underweight status at start of each treatment course was significantly associated with specific patterns of TRT. Influence of weight extremes on EFS and TRT is not set at diagnosis as previously reported but is moderated by subsequent weight status during intensive postinduction treatment phases. These observations suggest that weight is a potentially addressable risk factor to improve EFS and morbidity in pediatric ALL.
    Journal of Clinical Oncology 03/2014; 32(13). DOI:10.1200/JCO.2013.52.6962 · 17.88 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is responsible for ~90,000 cancer deaths/year, increasing cancer incidence and impairing its treatment. Obesity has also been shown to impact hematological malignancies, through as yet unknown mechanisms. Adipocytes are present in bone marrow and the microenvironments of many types of cancer, and have been found to promote cancer cell survival. In this review, we explore several ways in which obesity might cause leukemia treatment resistance. Obese patients may be at a treatment disadvantage due to altered pharmacokinetics of chemotherapy and dosage "capping" based on ideal body weight. The adipose tissue provides fuel to cancer cells in the form of amino acids and free fatty acids. Adipocytes have been shown to cause cancer cells to resist chemotherapy-induced apoptosis. In addition, obese adipose tissue is phenotypically altered, producing a milieu of pro-inflammatory adipokines and cytokines, some of which have been linked to cancer progression. Given the prevalence of obesity, understanding its role and adipose tissue in acute lymphoblastic leukemia treatment is necessary for evaluating current treatment regimen and revealing new therapeutic targets.
    Frontiers in Pediatrics 06/2014; 2:53. DOI:10.3389/fped.2014.00053