Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel: A population-based study

Shlomit Barzilai-Birenboim; Ronit Nirel; Nira Arad-Cohen; Galia Avrahami; Miri Ben Harush; Assaf Arie Barg; Bella Bielorai; Ronit Elhasid; Gil Gilad; Amos Toren; Sigal Weinreb; Shai Izraeli; Sarah Elitzur

doi:10.3390/cancers12102759

Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel: A population-based study

Shlomit Barzilai-Birenboim^*, Ronit Nirel, Nira Arad-Cohen, Galia Avrahami, Miri Ben Harush, Assaf Arie Barg, Bella Bielorai, Ronit Elhasid, Gil Gilad, Amos Toren, Sigal Weinreb, Shai Izraeli, Sarah Elitzur

^*Corresponding author for this work

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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.

Original language	American English
Article number	2759
Pages (from-to)	1-15
Number of pages	15
Journal	Cancers
Volume	12
Issue number	10
DOIs	https://doi.org/10.3390/cancers12102759
State	Published - Oct 2020

Bibliographical note

Funding Information:
Funding: This research was supported by the Israeli Society of Pediatric Hematology–Oncology, the Israel Cancer Association, and Amutat Chaim.

Funding Information:
This research was supported by the Israeli Society of Pediatric Hematology?Oncology, the Israel Cancer Association, and Amutat Chaim.The authors wish to acknowledge all pediatric hematology?oncology departments in Israel for their devoted care of these patients. Special thanks to Naomi Litichever and Dina Kugel, the data coordinators of the Israel National Study of Childhood ALL for their invaluable work, to Reut Rosen and Tali Shapiro of the Hebrew University for their help with the statistical analyses, and to Gloria Ganzach for her editing.

Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

Acute lymphoblastic leukemia
Hypertriglyceridemia
Risk factors
Sinus vein thrombosis
Thrombophilia
Venous thromboembolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers12102759

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Barzilai-Birenboim, S., Nirel, R., Arad-Cohen, N., Avrahami, G., Harush, M. B., Barg, A. A., Bielorai, B., Elhasid, R., Gilad, G., Toren, A., Weinreb, S., Izraeli, S., & Elitzur, S. (2020). Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel: A population-based study. Cancers, 12(10), 1-15. Article 2759. https://doi.org/10.3390/cancers12102759

@article{1d7fb9be94f04da29ef0a417bbae8106,

title = "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.",

keywords = "Acute lymphoblastic leukemia, Hypertriglyceridemia, Risk factors, Sinus vein thrombosis, Thrombophilia, Venous thromboembolism",

author = "Shlomit Barzilai-Birenboim and Ronit Nirel and Nira Arad-Cohen and Galia Avrahami and Harush, {Miri Ben} and Barg, {Assaf Arie} and Bella Bielorai and Ronit Elhasid and Gil Gilad and Amos Toren and Sigal Weinreb and Shai Izraeli and Sarah Elitzur",

note = "Funding Information: Funding: This research was supported by the Israeli Society of Pediatric Hematology–Oncology, the Israel Cancer Association, and Amutat Chaim. Funding Information: This research was supported by the Israeli Society of Pediatric Hematology?Oncology, the Israel Cancer Association, and Amutat Chaim.The authors wish to acknowledge all pediatric hematology?oncology departments in Israel for their devoted care of these patients. Special thanks to Naomi Litichever and Dina Kugel, the data coordinators of the Israel National Study of Childhood ALL for their invaluable work, to Reut Rosen and Tali Shapiro of the Hebrew University for their help with the statistical analyses, and to Gloria Ganzach for her editing. Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/cancers12102759",

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Barzilai-Birenboim, S, Nirel, R, Arad-Cohen, N, Avrahami, G, Harush, MB, Barg, AA, Bielorai, B, Elhasid, R, Gilad, G, Toren, A, Weinreb, S, Izraeli, S & Elitzur, S 2020, 'Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel: A population-based study', Cancers, vol. 12, no. 10, 2759, pp. 1-15. https://doi.org/10.3390/cancers12102759

TY - JOUR

T1 - Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel

T2 - A population-based study

AU - Barzilai-Birenboim, Shlomit

AU - Nirel, Ronit

AU - Arad-Cohen, Nira

AU - Avrahami, Galia

AU - Harush, Miri Ben

AU - Barg, Assaf Arie

AU - Bielorai, Bella

AU - Elhasid, Ronit

AU - Gilad, Gil

AU - Toren, Amos

AU - Weinreb, Sigal

AU - Izraeli, Shai

AU - Elitzur, Sarah

N1 - Funding Information: Funding: This research was supported by the Israeli Society of Pediatric Hematology–Oncology, the Israel Cancer Association, and Amutat Chaim. Funding Information: This research was supported by the Israeli Society of Pediatric Hematology?Oncology, the Israel Cancer Association, and Amutat Chaim.The authors wish to acknowledge all pediatric hematology?oncology departments in Israel for their devoted care of these patients. Special thanks to Naomi Litichever and Dina Kugel, the data coordinators of the Israel National Study of Childhood ALL for their invaluable work, to Reut Rosen and Tali Shapiro of the Hebrew University for their help with the statistical analyses, and to Gloria Ganzach for her editing. Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2020/10

Y1 - 2020/10

N2 - 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.

AB - 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.

KW - Acute lymphoblastic leukemia

KW - Hypertriglyceridemia

KW - Risk factors

KW - Sinus vein thrombosis

KW - Thrombophilia

KW - Venous thromboembolism

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U2 - 10.3390/cancers12102759

DO - 10.3390/cancers12102759

M3 - Article

AN - SCOPUS:85091599328

SN - 2072-6694

VL - 12

SP - 1

EP - 15

JO - Cancers

JF - Cancers

IS - 10

M1 - 2759

ER -

Venous thromboembolism and its risk factors in children with acute lymphoblastic leukemia in israel: A population-based study

Abstract

Bibliographical note

Keywords

UN SDGs

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