Saskia Prasca1, Roxana Carmona2, Lingyun Ji3, Richard H Ko4, Deepa Bhojwani5, Yasmin A Rawlins6, Steven D Mittelman7, Guy Young8, Etan Orgel9. 1. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA. 2. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA. Electronic address: rcarmona@chla.usc.edu. 3. Department of Preventive Medicine, USC Norris Comprehensive Cancer Center, 1441 Eastlake Ave, Los Angeles, 90033, CA, USA. Electronic address: lingyun.ji@med.usc.edu. 4. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA; Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, 90033, CA, USA. 5. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA; Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, 90033, CA, USA. Electronic address: dbhojwani@chla.usc.edu. 6. College of Physicians and Surgeons, Columbia University, 630 W 168th St, New York, 10032, NY, USA. Electronic address: yar2111@cumc.columbia.edu. 7. Center for Endocrinology, Diabetes & Metabolism, Children's Hospital Los Angeles, Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA. Electronic address: smittelman@mednet.ucla.edu. 8. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA; Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, 90033, CA, USA. Electronic address: gyoung@chla.usc.edu. 9. Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, 90027, CA, USA; Keck School of Medicine, University of Southern California, 1975 Zonal Ave, Los Angeles, 90033, CA, USA. Electronic address: eorgel@chla.usc.edu.
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.
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.
Authors: Zachary E West; Sharon M Castellino; Caitlin Monroe; Amanda S Thomas; Courtney McCracken; Tamara P Miller Journal: Leuk Lymphoma Date: 2020-12-01