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Obesity and risk for venous thromboembolism from contemporary therapy for pediatric acute lymphoblastic leukemia.

ABSTRACT: INTRODUCTION:Acute lymphoblastic leukemia (ALL) therapy confers risk for venous thromboembolism (VTE) and associated acute and long-term morbidity. Obesity increases VTE risk in the general population but its impact on ALL therapy-associated VTE is unknown. METHODS:In a retrospective cohort of children treated for ALL between 2008 and 2016 (n?=?294), we analyzed obesity at diagnosis (body mass index [BMI] ?95%) and subsequent development of VTE. A subset participated in two concurrent prospective ALL trials studying body composition via dual-energy X-ray absorptiometry (DXA) (n?=?35) and hypercoagulability via thromboelastography (TEG) (n?=?46). Secondary analyses explored whether precise measurement of body fat and/or global hemostasis ex vivo by TEG could further delineate VTE risk in the obese. RESULTS:Overall, we found 27/294 (9.2%) patients developed symptomatic VTE during therapy, 19/27 (70%) occurred during Induction. Study-defined "serious" VTE developed in 4/294 (1.4%) of patients. Obesity but not overweight was strongly predictive of symptomatic VTE (obesity odds ratio?=?3.8, 95% confidence interval 1.5-9.6, p?=?0.008). In the DXA subset, only 2/35 patients developed symptomatic VTE. However, within those prospectively screened during Induction, 30% (14/46) developed VTE; eight (17%) of these were asymptomatic and found only via screening. CONCLUSIONS:In this pediatric ALL cohort, obesity conferred more than a three-fold increased risk for symptomatic VTE. In a subgroup of patients who underwent active screening, up to a third were noted to have VTE (symptomatic and asymptomatic). TEG did not predict VTE. Additional studies are necessary to validate these findings and to further refine a risk-stratified approach to thrombo-prevention during ALL therapy.

SUBMITTER: Prasca S

PROVIDER: S-EPMC7522001 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Project description:Background:Infection is the most important cause of treatment-related morbidity and mortality in pediatric patients treated for acute lymphoblastic leukemia (ALL). Although routine in adults with leukemia, antibacterial prophylaxis is controversial in pediatrics because of insufficient evidence for its efficacy or antibiotic choice and concerns about promoting antibiotic resistance and Clostridium difficile infection. Methods:This was a single-center, observational cohort study of patients with newly diagnosed ALL, comparing prospectively collected infection-related outcomes in patients who received no prophylaxis, levofloxacin prophylaxis, or other prophylaxis during induction therapy on the total XVI study. A propensity score-weighted logistic regression model was used to adjust for confounders. Results:Of 344 included patients, 173 received no prophylaxis, 69 received levofloxacin prophylaxis, and 102 received other prophylaxis regimens. Patients receiving prophylaxis had longer duration of neutropenia. Prophylaxis reduced the odds of febrile neutropenia, likely bacterial infection, and bloodstream infection by ?70%. Levofloxacin prophylaxis alone reduced these infections, but it also reduced cephalosporin, aminoglycoside, and vancomycin exposure and reduced the odds of C. difficile infection by >95%. No increase in breakthrough infections with antibiotic-resistant organisms was seen, but this cannot be excluded. Conclusions:This is the largest study to date of antibacterial prophylaxis during induction therapy for pediatric ALL and the first to include a broad-spectrum fluoroquinolone. Prophylaxis prevented febrile neutropenia and systemic infection. Levofloxacin prophylaxis also minimized the use of treatment antibiotics and drastically reduced C. difficile infection. Although long-term antibiotic-resistance monitoring is needed, these data support using targeted prophylaxis with levofloxacin in children undergoing induction chemotherapy for ALL. Clinical Trials Registration:NCT00549848.

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Obesity and risk for venous thromboembolism from contemporary therapy for pediatric acute lymphoblastic leukemia.

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