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Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study.

ABSTRACT: Venous thromboembolism (VTE) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. The aim of this population-based study was to evaluate the rate, risk factors, and long-term sequelae of VTE in children treated for ALL. The cohort included 1191 children aged 1-19 years diagnosed with ALL between 2003-2018, prospectively enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009. VTEs occurred in 89 patients (7.5%). Long-term sequelae were uncommon. By univariate analysis, we identified four significant risk factors for VTEs: Severe hypertriglyceridemia (p = 0.005), inherited thrombophilia (p < 0.001), age >10 years (p = 0.015), and high-risk ALL group (p = 0.039). In addition, the incidence of VTE was significantly higher in patients enrolled in AIEOP-BFM ALL 2009 than in those enrolled in ALL-IC BFM 2002 (p = 0.001). Severe VTE occurred in 24 children (2%), all of whom had at least one risk factor. Elevated triglyceride levels at diagnosis did not predict hypertriglyceridemia during therapy. In a multivariate analysis of 388 children, severe hypertriglyceridemia and inherited thrombophilia were independent risk factors for VTE. Routine evaluation for these risk factors in children treated for ALL may help identify candidates for intervention.

SUBMITTER: Barzilai-Birenboim S

PROVIDER: S-EPMC7600511 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study.

Barzilai-Birenboim Shlomit S Nirel Ronit R Arad-Cohen Nira N Avrahami Galia G Ben Harush Miri M Barg Assaf Arie AA Bielorai Bella B Elhasid Ronit R Gilad Gil G Toren Amos A Weinreb Sigal S Izraeli Shai S Elitzur Sarah S

Cancers 20200925 10

Venous thromboembolism (VTE) is a serious complication of acute lymphoblastic leukemia (ALL) therapy. The aim of this population-based study was to evaluate the rate, risk factors, and long-term sequelae of VTE in children treated for ALL. The cohort included 1191 children aged 1-19 years diagnosed with ALL between 2003-2018, prospectively enrolled in two consecutive protocols: ALL-IC BFM 2002 and AIEOP-BFM ALL 2009. VTEs occurred in 89 patients (7.5%). Long-term sequelae were uncommon. By univa ...[more]

PMID: 32992771

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Project description:ImportanceIt is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE).ObjectiveTo estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism.Design, setting, and participantsThis study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018.ExposuresA panel of several established cardiovascular risk factors.Main outcomes and measuresHazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI).ResultsOf the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers.Conclusions and relevanceOlder age, smoking, and adiposity were consistently associated with higher VTE risk.

Project description:ImportanceThe size of the risk of recurrent venous thromboembolism (VTE) after surgery in patients with a history of VTE is not well known.ObjectivesTo estimate the risk of and to identify the factors associated with recurrent VTE in patients undergoing surgery who have a history of VTE.Design, setting, and participantsThis population-based, follow-up cohort study includes patients with VTE who participated in the Multiple Environment and Genetic Assessment (MEGA) study. Original data were collected from March 1999 to April 2010. Data analysis began in June 1999 and ended in April 2010.ExposuresSurgery following a first VTE.Main outcomes and measurementsKaplan-Meier analyses were used to estimate cumulative incidences of recurrent VTE. Cox regression with a time-dependent covariate (surgery) was used to calculate the hazard ratio (HR) for developing recurrent VTE after surgery compared with no surgery.ResultsOverall, 3741 patients (mean [SD] age, 48.4 [12.8] years; 2020 [54.0%] women) with a history of VTE were included in the analysis, amounting to 18 899 person-years, with a median (interquartile range) follow-up of 5.7 (3.0-7.2) years. Of the 3741 patients, 580 (15.5%) underwent surgery and 601 (16.1%) developed a recurrent thrombotic event. The 1-month cumulative incidence of recurrent VTE for all surgery types was 2.1% (95% CI, 1.2%-3.6%), which increased to 3.3% (95% CI, 2.1%-5.1%) at 3 months and 4.6% (95% CI, 3.1%-6.6%) at 6 months. At 6 months, risk of recurrent VTE ranged from 2.3% to 9.3%, depending on surgery type. In addition to surgery type, factor V Leiden mutation (HR, 3.4; 95% CI, 1.6-7.4) and male sex (HR, 2.7; 95% CI, 1.3-5.8) were associated with increased risk of recurrent VTE.Conclusions and relevanceSurgery was associated with an increased risk of recurrent VTE in patients with a history of VTE; risk remained high for up to 6 months after the procedure. This study suggests that high-risk individuals may be identified based on surgery type, sex, and the presence of factor V Leiden mutation. These findings stress the need for revision of the current thromboprophylactic approach to prevent recurrence in these patients.

Project description:Leukemia is the most common type of cancer among children and adolescents worldwide. The aim of this umbrella review was (1) to provide a synthesis of the environmental risk factors for the onset of childhood acute lymphoblastic leukemia (ALL) by exposure window, (2) evaluate their strength of evidence and magnitude of risk, and as an example (3) estimate the prevalence in the German population, which determines the relevance at the population level. Relevant systematic reviews and pooled analyses were identified and retrieved through PubMed, Web of Science databases and lists of references. Only two risk factors (low doses of ionizing radiation in early childhood and general pesticide exposure during maternal preconception/pregnancy) were convincingly associated with childhood ALL. Other risk factors including extremely low frequency electromagnetic field (ELF-MF), living in proximity to nuclear facilities, petroleum, benzene, solvent, and domestic paint exposure during early childhood, all showed some level of evidence of association. Maternal consumption of coffee (high consumption/>2 cups/day) and cola (high consumption) during pregnancy, paternal smoking during the pregnancy of the index child, maternal intake of fertility treatment, high birth weight (≥4000 g) and caesarean delivery were also found to have some level of evidence of association. Maternal folic acid and vitamins intake, breastfeeding (≥6 months) and day-care attendance, were inversely associated with childhood ALL with some evidence. The results of this umbrella review should be interpreted with caution; as the evidence stems almost exclusively from case-control studies, where selection and recall bias are potential concerns, and whether the empirically observed association reflect causal relationships remains an open question. Hence, improved exposure assessment methods including accurate and reliable measurement, probing questions and better interview techniques are required to establish causative risk factors of childhood leukemia, which is needed for the ultimate goal of primary prevention.

Dataset Information

Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study.

Publications

Venous Thromboembolism and Its Risk Factors in Children with Acute Lymphoblastic Leukemia in Israel: A Population-Based Study.

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