Incidence and Risk Factors of Venous Thromboembolism in Childhood Acute Lymphoblastic Leukaemia – a Population-Based Analysis of the Austrian Berlin-Frankfurt-Münster (BFM) Study Group

Gidl, Anna; Füreder, Anna; Benesch, Martin; Dworzak, Michael; Engstler, Gernot; Jones, Neil D.; Kropshofer, Gabriele; Pötschger, Ulrike; Poyer, Fiona; Tamesberger, Melanie; Witt, Volker; Mann, Georg; Attarbaschi, Andishe

doi:10.1080/08880018.2022.2089791

Cited by 3 publications

(5 citation statements)

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“…Regarding risk factors for developing thromboembolic complications during therapy, patients with ALL and ≥ 10.0 years of age who are treated according to the BFM regimen are particularly affected (compared to JACLS – Japan Association of Childhood Leukemia Study ALL-02 protocol) [ 13 ]. Adolescent age (10–16 or 10–18 years, retrospectively) was also reported by other authors to be a main risk factor for the development of thromboembolic events [ 17 ], as this patient cohort shows a more severe decline in anticoagulant and fibrinolytic parameters [ 18 ]. Furthermore, obese pediatric ALL patients showed a three-fold increased risk of developing a thromboembolic complication (symptomatic or asymptomatic) [ 19 ].…”

Section: Discussionmentioning

confidence: 58%

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Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years

Salvador,

Kropshofer

et al. 2024

Thrombosis J

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Background Thromboembolic complications are well known in the treatment of childhood acute lymphoblastic leukemia. Over the years it has not been possible to reach a consensus on a possible prophylaxis of thromboembolic events during intensive therapy. Only the administration of enoxaparin was able to achieve evidence in the literature to date. Methods In this retrospective study, 173 childhood leukemia patients were treated over 20 years with a thromboembolic prophylaxis including enoxaparin and AT III during induction therapy with L-asparaginase and cortisone. Results We here report the effectiveness of administration of enoxaparin and AT III in childhood leukemia, showing a strikingly low prevalence of deep vein thrombosis (2.9%). Especially in adolescent patients, a particularly great need for AT III was demonstrated. Conclusions We recommend thromboembolic prophylaxis with enoxaparin and AT III substitution during induction/reinduction therapy with L-asparaginase and glucocorticosteroids, especially from adolescence onwards.

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Section: Discussionmentioning

confidence: 58%

“…As early as 2008, our department was able to demonstrate a 12.7% frequency of deep vein thrombosis in a historical cohort of 71 pediatric ALL patients, who were treated according to the AIEOP-BFM 95/2000 protocols [ 6 ]. A newer study from Austria [ 17 ] finally showed an incidence of thromboembolic events (≥ grade 2) of < 5%.…”

Section: Discussionmentioning

confidence: 99%

Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years

Salvador,

Kropshofer

et al. 2024

Thrombosis J

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“…A retrospective evaluation of the LAL-SEHOP-PETHEMA-2013 Spanish protocol showed a VTE incidence of 8.7% 10 . According to other series, family history of thrombosis, presence of mediastinal mass, high-risk treatment group and inherited thrombophilia were statistically significant risk factors 2,[10][11][12][13][14][15][16][17][18][19][20] . Of note, almost all VTE in this series were diagnosed during induction to remission phase, where asparaginase (ASP) and corticosteroids (CS) are demonstrated to have an important role in the hemostatic balance 10,11,15,17,18,21 .…”

Section: Introductionmentioning

confidence: 83%

“…10 According to other series, family history of thrombosis, presence of mediastinal mass, high-risk treatment group, and inherited thrombophilia were statistically significant risk factors. 2 10 11 12 13 14 15 16 17 18 19 20 Of note, almost all VTE cases in this series were diagnosed during induction to remission phase, where asparaginase (ASP) and corticosteroids (CSs) are demonstrated to have an important role in the hemostatic balance. 10 11 15 17 18 21 CSs induce an increment of procoagulant factors and induce a hypofibrinolytic state increasing plasminogen activator inhibitor-1.…”

Section: Introductionmentioning

confidence: 95%

“…2 10 11 12 13 14 15 16 17 18 19 20 Of note, almost all VTE cases in this series were diagnosed during induction to remission phase, where asparaginase (ASP) and corticosteroids (CSs) are demonstrated to have an important role in the hemostatic balance. 10 11 15 17 18 21 CSs induce an increment of procoagulant factors and induce a hypofibrinolytic state increasing plasminogen activator inhibitor-1. 3 16 All different ASP formulations ( Escherichia coli ASP, Erwinia -derived ASP, and polyethylene glycosylated E. coli -asparaginase [PEG-ASP]) led to a decrease of the hepatic synthesis of physiological anticoagulants antithrombin (AT), protein C (PC), and protein S (PS).…”

Section: Introductionmentioning

confidence: 95%

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Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia

Ruiz-Llobet,

Gassiot,

Sarrate

et al. 2024

Thromb Haemost

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Background: Venous thromboembolism (VTE) etiology in children with acute lymphoblastic leukemia (ALL) is multifactorial. The use of global assays of hemostasis as thrombin generation test (TGT) is useful to individualize VTE risk in adult patients. The aim of this prospective cohort study was to evaluate the usefulness of an automated TGT to evaluate VTE risk during ALL treatment in children. Methods: TGT (automated analyzer ST Genesia; ThromboScreen) and pro and anticoagulant plasma proteins were analyzed during ALL treatment in pediatric patients following LAL-SEHOP-PETHEMA-2013 guidelines. Results were compared with a series of pediatric normal controls and evaluated according to pegylated asparaginase PEG-ASP administration and to VTE risk factors. Results: The study included 67 patients: males n=35, B-ALL (n=60). None had a VTE during the evaluated period. Compared to healthy controls, normalized endogenous thrombin potential (N-ETP) ratio in patients was higher and ETP inhibition (ETP-inh) was lower, especially after PEG-ASP administration. Plasmatic protein C and protein S levels decreased after PEG-ASP administration, but antithrombin mean level did not. A bivariant analysis showed that ETP-inh was lower in patients >10-year-old (p=0.05) and in those with non-O blood type (p=0.005). A linear mixed model also showed a higher TGT prothrombotic profile in patients with inherited thrombophilia. Conclusions: TGT could be a biomarker of a high VTE risk in ALL pediatric patients. Patients > 10 years, of non-O blood group and with inherited thrombophilia were associated with a significantly higher thrombotic profile, and an increased profile was also observed after administration of PEG-ASP.

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Central venous access device adverse events in pediatric patients with cancer: a systematic review and meta-analysis

Nunn,

Takashima,

Wray-Jones

et al. 2024

Support Care Cancer

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Purpose To systematically review the proportion and incidence of CVAD-associated complications in pediatric patients with cancer. Methods PubMed, Embase, and the Cumulative Index of Nursing and Allied Health Literature were searched from 2012 to 2022. Cohort studies and the control arm of randomized controlled trials, which reported CVAD-associated complications in pediatric patients aged 0–18 years, were included. CVAD complications were defined as CVAD failure, central line–associated bloodstream infection (CLABSI), local infection, occlusion, CVAD-associated venous thromboembolism, dislodgement/migration, breakage/rupture, and dehiscence. The pooled proportion and incidence rate (IR) for each CVAD-associated complication were reported. Results Of 40 included studies, there was mixed quality of methods and reporting. Approximately 31.4% (95% confidence interval [CI] 22.5–41.1; 6920 devices) of devices experienced a CVAD-associated complication, and 14.8% (95% CI 10.2–20.1; 24 studies; 11,762 devices) of CVADs failed before treatment completion (incidence rate (IR) of 0.5 per 1000 catheter days (95% CI 0.3–0.8; 12 studies; 798,000 catheter days)). Overall, 21.2% (95% CI 14.3–28.9; 26 studies; 5054 devices) of CVADs developed a CLABSI, with an IR of 0.9 per 1000 catheter days (95% CI 0.6–1.3; 12 studies; 798,094 catheter days). Tunneled central venous catheters (TCVC) and peripherally inserted central catheters (PICCs) were associated with increased complications in comparison to totally implanted venous access devices (TIVADs). Conclusion CVAD complication rates in this population remain high. TCVCs and PICCs are associated with increased complications relative to TIVADs. Insufficient evidence exists to guide device selection in this cohort, necessitating further research to determine the role of PICCs in pediatric cancer care. PROSPERO: CRD42022359467. Date of registration: 22 September 2022.

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Incidence and Risk Factors of Venous Thromboembolism in Childhood Acute Lymphoblastic Leukaemia – a Population-Based Analysis of the Austrian Berlin-Frankfurt-Münster (BFM) Study Group

Cited by 3 publications

References 27 publications

Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years

Prophylaxis with enoxaparin and antithrombin III in drug-induced coagulation alterations in childhood leukemia: a retrospective experience of 20 years

Thrombin Generation Profile Using ST-Genesia after PEG-asparaginase in Pediatric Patients with Acute Lymphoblastic Leukemia

Central venous access device adverse events in pediatric patients with cancer: a systematic review and meta-analysis

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