Venous thromboembolism incidence and risk factors in adults with acute lymphoblastic leukemia treated with and without pegylated E. coli asparaginase-containing regimens

2021 ◽  
Author(s):  
Sarah M. Kashanian ◽  
Noa G. Holtzman ◽  
Ciera L. Patzke ◽  
Jonathan Cornu ◽  
Alison Duffy ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
E Coli

Risk factors for symptomatic venous thromboembolism during therapy for childhood acute lymphoblastic leukemia

2019 ◽  
Vol 178 ◽  
pp. 132-138 ◽  
Author(s):  
M.K. Mateos ◽  
T.N. Trahair ◽  
C. Mayoh ◽  
P.M. Barbaro ◽  
R. Sutton ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia

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

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2759
Author(s):  
Shlomit Barzilai-Birenboim ◽  
Ronit Nirel ◽  
Nira Arad-Cohen ◽  
Galia Avrahami ◽  
Miri Ben Harush ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Population Based ◽  
Population Based Study ◽  
Inherited Thrombophilia ◽  
Severe Hypertriglyceridemia

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.

The Development Of Venous Thromboembolism May Increase The Risk Of Osteonecrosis In Children With Acute Lymphoblastic Leukemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3864-3864
Author(s):  
Badhiwala H. Jetan ◽  
Trishana Nayiager ◽  
Uma H. Athale
Keyword(s):  
Risk Factors ◽  
Logistic Regression ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Older Age ◽  
Regression Analyses ◽  
Female Ratio ◽  
Increased Risk ◽  
The Impact

Abstract Background Osteonecrosis (ON) is a severely disabling complication of anti-leukemic therapy, specifically long-term corticosteroid use. A hypercoagulable state is thought to underlie corticosteroid-related ON. Children with acute lymphoblastic leukemia (ALL) are also at increased risk of venous thromboembolism (VTE), indicating underlying hypercoagulability in this disease entity. Hence, we explored the relationship between ON and VTE, along with the association of ON with other variables, including age and asparaginase (ASP) therapy, in children with ALL. Methods Health records of children (< 18 yrs.) with de novo ALL treated at McMaster Children’s Hospital from 1992 to 2010 were reviewed. Patients were treated according to Dana-Farber Cancer Institute (DFCI) ALL Consortium Protocols. Data regarding demographics, leukemia diagnosis and therapy, development and characteristics of ON and VTE, and thrombophilia work-up, if any, were collected from computer records and chart review. Osteonecrosis was diagnosed by plain X-ray, computed tomography (CT), magnetic resonance (MR) imaging, and/or technetium-99m (99mTc) bone scan. We included ON diagnosed during therapy and/or at any point during post-treatment follow-up. Standard radiological measures, including venous Doppler ultrasound and/or venography (conventional, CT, MR), confirmed VTE. We included only clinically significant thromboembolic events, defined as symptomatic VTE, or asymptomatic VTE requiring anticoagulation, developing during ALL therapy. Logistic regression analyses were performed to identify possible predictors of ON. Odds ratios (ORs) with 95% confidence intervals (CIs) and corresponding p-values were determined. Results Mean age of the study cohort (n = 208) was 5.4 years and male/female ratio 1.2:1. Seventy-eight (37.5%) patients had high-risk (HR) ALL and 127 (61.1%) received dexamethasone (DEX) as post-induction steroid. One hundred and sixty-two (77.9%) patients received E. coli ASP, 19 (9.1%) Erwinia ASP, and 27 (13.0%) PEG ASP. Twenty-one (10.1%) children developed ON. Joints affected by ON included the ankle in 11 subjects, knee in 10, hip in 8, and heel in one. Fourteen of the 21 patients (66.7%) had involvement of more than one joint. All patients were diagnosed with ON during ALL treatment, with the average being 69.2 weeks following ALL diagnosis. Forty-two (20.2%) subjects had a VTE while receiving therapy at an average of 29.4 weeks after ALL diagnosis. Nine patients had cerebral sinovenous thrombosis, 7 deep vein thrombosis (DVT), and one pulmonary embolism (PE). Twenty-six patients developed a central venous line (CVL)-related VTE. Results of univariate logistic regression analyses for osteonecrosis are presented in Table 1. VTE strongly predicted development of ON – OR 8.85 (95% CI 3.37–23.25, p< 0.001). Thirteen (31.0%) patients with VTE developed ON compared to 8 (4.8%) of 166 subjects without VTE. In 10 of 13 (76.9%) patients who developed both VTE and ON, the diagnosis of VTE preceded that of ON. Given that older age is a known risk factor for both VTE and ON, we conducted a multivariate analysis, which confirmed that age, ASP type, and VTE were independent, significant risk factors for ON (Table 2). Conclusion In addition to the known impact of older age, we identified VTE and type of ASP as independent risk factors for ON in children with ALL. These observations suggest overlap in the etiopathogenesis of ON and VTE. We recommend larger, prospective studies to confirm the association of VTE and PEG ASP with ON and to assess the impact of hypercoagulability on the development of ON. This in turn may help develop preventive strategies (e.g., thromboprophylaxis) for ALL-associated ON. Disclosures: No relevant conflicts of interest to declare.

Venous Thromboembolism in Children with Acute Lymphoblastic Leukemia in Northern Europe

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3652-3652
Author(s):  
Nadine Gretenkort Andersson ◽  
Susanna Ranta ◽  
Tony Frisk ◽  
Maria Winther Gunnes ◽  
Jon Helgestad ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
High Risk ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Risk Treatment ◽  
The Impact ◽  
All Treatment

Abstract Introduction Children with acute lymphoblastic leukemia (ALL) are at high risk for VTE due to several thrombotic risk factors such as the disease itself, central venous line (CVL), immobilization, infections and treatment with asparaginase and steroids, leading to increased morbidity and mortality. Identifying the clinical risk factors and high risk treatment phases for VTE is important and can lead to a better outcome and quality of life for these children. We conducted this prospective study on symptomatic VTE in children with ALL to characterize the prevalence, the clinical characteristics, and potential clinical predictive factors for symptomatic VTE and the impact of thrombosis on treatment delays. Methods All patients (n=1083), age 1-18 years, diagnosed with B-cell precursor or T-cell ALL between June 2008 and July 2013 and enrolled in the NOPHO ALL 2008 treatment protocol in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), Estonia or Lithuania were included in the study. Thrombotic events (TE) were prospectively recorded until the end of December 2013. TE was defined as objectively confirmed symptomatic TE. Main questions were: time of VTE occurrence, impact on treatment delay, type of CVL, dysfunction of the CVL, blood samples including D-dimers and thrombophilia screening, family history of TE, type and duration of antithrombotic therapy, and major bleeding during anticoagulation. Results The cumulative risk of symptomatic VTE was 6.0% (CI 95% 4.7-7.7) for children treated with the NOPHO- ALL 2008 protocol. No arterial TE was found. VTE occurred in median 80 (IQR 43-118) days in the SR and 104 (IQR 39-127) days in the IR protocol and were in majority of cases associated with asparaginase treatment (84.5%, 49/58). See figure 1 for the localization of the VTE. VTE had a high impact on the treatment in the patients. Treatment with asparaginase was shortened in half of patients with VTE and chemotherapy treatment delayed in 25%. Age ≥ 15 years and residual disease ≥ 5% after induction therapy was significantly associated with VTE in the multivariate analysis (Table 1). Conclusions Our findings indicate that Venous Thromboembolism (VTE): - is a major complication of ALL treatment - may lead to reduced intensity of the ALL treatment and subsequently possible long term impact on the EFS - risk is dependent on the patients age and residual disease after leukemia induction The possibility of identifying patients with elevated risk of VTE needs to be studied further and thromboprophylaxis for such patients during high-risk treatment phases can be considered in future ALL protocols. Table 1. Multivariate Cox regression analysis of the risk for VTE Factor HR (95% CI) P value Age category, years 1-7 8-14 15-17 Ref1.9 (1.0-3.7)6.2 (3.4-11.3) <0.000 0.044 0.000 Gender Male 1.6 (0.9-2.8) 0.074 ALL phenotype B-precursor T-cell Bilineage Ref2.3 (1.2-4.2)4.2 (1.0-17.4) 0.019 0.010 0.047 Residual disease ≥ 5% day 29 4.1 (1.9-9.0) 0.001 Figure 1. Localization of VTE Figure 1. Localization of VTE Disclosures No relevant conflicts of interest to declare.

Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration

Blood ◽  
2003 ◽  
Vol 101 (7) ◽  
pp. 2529-2533 ◽  
Author(s):  
Ulrike Nowak-Göttl ◽  
Elvira Ahlke ◽  
Gudrun Fleischhack ◽  
Dirk Schwabe ◽  
Rosmarie Schobess ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Therapy ◽  
Lymphoblastic Leukemia ◽  
Treatment Modalities ◽  
Thromboembolic Events ◽  
Increased Risk ◽  
Significant Difference ◽  
Prothrombotic Risk Factors

Alterations in hemostasis leading to symptomatic thromboembolism have been observed in patients with acute lymphoblastic leukemia (ALL) receiving Escherichia coli asparaginase (CASP) combined with steroids. Moreover, hereditary prothrombotic risk factors are associated with an increased risk for venous thromboembolism in pediatric ALL patients treated according to the BFM 90/95 protocols (including CASP combined with prednisone during induction therapy). To assess whether the thromboembolic risk associated with established prothrombotic risk factors is modified by treatment modalities (prednisone or dexamethasone), the present analysis was performed. Three hundred thirty-six consecutively recruited leukemic children treated according to different BFM protocols (PRED group, n = 280, 60 mg/m2 prednisone; DEXA group, n = 56, 10 mg/m2 dexamethasone during induction therapy) were studied. Study end point was the onset of symptomatic vascular accidents during induction therapy. Cumulative thromboembolism-free survival was significantly reduced in children in the PRED group (thrombosis frequency, 10.4%) compared with children in the DEXA group (thrombosis frequency, 1.8%; P = .028). Although no significant difference was found in the overall prevalence of prothrombotic risk factors, 46.5% of patients in the PRED group who experienced thromboembolic events were carriers of a prothrombotic risk factor, whereas no carrier in the DEXA group had a thromboembolism. At the time of maximum CASP activity, fibrinogen and activities of antithrombin, plasminogen, and protein S were significantly reduced in the PRED group. No significant correlation could be found between CASP activity and levels of coagulation factors. In conclusion, the use of dexamethasone instead of prednisone, administered with CASP, significantly reduced the onset of venous thromboembolism.

scholarly journals Venous thromboembolism in a large cohort of children with acute lymphoblastic leukemia: Risk factors and effect on prognosis

2019 ◽  
Vol 3 (2) ◽  
pp. 234-241 ◽  
Author(s):  
Irene L. M. Klaassen ◽  
Mandy N. Lauw ◽  
Marta Fiocco ◽  
Inge M. van der Sluis ◽  
Rob Pieters ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Large Cohort

Incidence, characteristics, and risk factors of venous thromboembolism in adolescent and young adult acute lymphoblastic leukemia patients receiving peg-asparaginase.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18520-e18520
Author(s):  
Brynne Underwood ◽  
Qiuhong Zhao ◽  
Alison R. Walker ◽  
Alice S. Mims ◽  
Sumithira Vasu ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Regression Models ◽  
Lymphoblastic Leukemia ◽  
Adolescent And Young Adult ◽  
Hazard Ratios ◽  
Adolescent And Young Adults ◽  
Male Sex

e18520 Background: Venous thromboembolism (VTE) is common in acute lymphoblastic leukemia (ALL) patients (pts) receiving peg-asparaginase (ASNase) however there is limited data regarding the incidence of VTE and risk factors for VTE in adolescent and young adults (AYA) treated with ASNase. Methods: This is a single institutional retrospective analysis of AYA pts with ALL who received ASNase from January 2013 to December 2018. Time to VTE was calculated from date of starting treatment to onset of VTE or censored at last assessment date, treating death as a competing risk. The cumulative incidence of VTE was estimated and the Fine and Gray regression models accounting for competing risks were used to examine the association between risk factors and VTE. Results: Forty-six AYA ALL patients were included. Pt characteristics are shown in the Table. Twenty pts had a VTE following ASNase with the cumulative incidence rate of 35% (95% CI: 22-48%) at 100 days. The most common VTE sites were cerebral (n=6) and upper extremity (n=6). Nine pts (43%) had at least one recurrent VTE. After initial VTE, ASNase was continued in 13 pts (62%), stopped in 6 pts (29%), and dose reduced in 2 pts (10%). Nine pts (45%) of those who developed VTE received antithrombin. Out of the 6 pts with VTE who had ASNase discontinued or dose reduced, 2 (33%) had progression of ALL. The hazard ratios (HR) for risk of VTE from univariable regression models are listed in Table 1. Male sex was associated with increased VTE risk, with HR=3.33 (95% CI: 1.13-9.77). Conclusions: Our study estimated the incidence of VTE in the AYA cohort. Only male sex was identified as a risk factor for VTE. Additional studies are needed to assess VTE risk factors in AYA pts with ALL. Pt characteristics and hazard ratios for risk of VTE. [Table: see text]

ALL-414: Obesity is Not Associated with an Increased Risk of Venous Thromboembolism in AYA Patients with Acute Lymphoblastic Leukemia

2021 ◽  
Vol 21 ◽  
pp. S276
Author(s):  
Sandra Renee Jones ◽  
Roshni Bharati Patel ◽  
Mahvish Qureshi Rahim ◽  
Sandra K. Althouse ◽  
Sandeep Batra
Keyword(s):  
Venous Thromboembolism ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Increased Risk

Incidence and risk factors for hypoglycemia during maintenance chemotherapy in pediatric acute lymphoblastic leukemia

2021 ◽  
Author(s):  
Elizabeth Rosenfeld ◽  
Kelly D. Getz ◽  
Tamara P. Miller ◽  
Alix E. Seif ◽  
Brian T. Fisher ◽  
...  
Keyword(s):  
Risk Factors ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Maintenance Chemotherapy ◽  
Pediatric Acute Lymphoblastic Leukemia
Sign in / Sign up

Export Citation Format

Share Document