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.
"The association between obesity and leukemia prognosis has also been examined in many studies, with some detecting an effect of obesity to worsen prognosis, and others not (Table 1). Two of the studies acknowledged that their failure to detect an association between BMI and ALL outcome may have been due to small sample size (16, 17). Interestingly, the risk estimates of overall survival and event-free survival from both studies showed a trend of worsened outcome in the overweight/obese patients. "
[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
[Show abstract][Hide abstract] ABSTRACT: The 5-year survival rates for childhood ALL are approaching 80%, but therapy-related toxicities are common. One of the challenges in this population is determining the most efficacious therapeutic regimens for these individuals. Factors such as drug metabolism, genetics, and concomitant disease affect drug efficacy and may be important in determining therapeutic outcomes in these patients. This review will focus on these factors in the treatment of childhood ALL.
[Show abstract][Hide abstract] ABSTRACT: Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hyperglycemic during induction chemotherapy have an increased risk for infection during their first year of treatment.
We conducted a retrospective chart review of 135 patients diagnosed with ALL during 1999-2001 at Texas Children's Hospital. Infectious outcomes during the first year of therapy were compared in three groups patients based on blood glucose concentrations during induction therapy: euglycemic (<140 mg/dl), mild hyperglycemic (MH) (140-199 mg/dl) and overt hyperglycemic (OH) (blood glucose >200 mg/dl).
Seventy-five (56%) patients met criteria for either MH (21%) or OH (35%). Hyperglycemia was more prevalent in older children (P < 0.001) and those at risk for being overweight (BMI% >85%) at diagnosis (P < 0.01). Patients with MH and OH were 2.5 times (95% CI 1.0-6.2) and 2.1 times (95% CI 1.0-4.6) more likely to have documented infections, respectively. Patients with OH were 4.2 times (95% CI 1.5-12) more likely to have bacteremia/fungemia, 3.8 times (95% CI 1.2-11.6) more likely to have cellulitis, and 4.0 times (95% CI 1.7-9.3) more likely to be admitted for fever and neutropenia than the euglycemia group.
Hyperglycemia, especially when overt, may be a previously unrecognized risk factor of infectious complications in children with ALL during the first year of treatment.
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