Derivation and external validation of a venous thromboembolism risk prediction model in asparaginase-treated ALL

The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation cohort. A risk prediction model for VTE at 30 days was derived using variables with P value < .05 in the multivariable model and was tested in the validation cohort. VTE risk factors on multivariable analysis in the derivation cohort included D-dimer ≥1 μg fibrinogen equivalent unit per mL (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.07-6.5) and hemoglobin (HR for each 1 g/dL increment, 1.19; 95% CI, 1.06-1.34) at ALL diagnosis. A VTE risk score based on these variables distinguished between a 4% (95% CI, 0.72-12) and 20% (95% CI, 14-27) 30-day cumulative incidence of VTE in the derivation cohort, with similar findings in the validation cohort (area under the curve, 0.56). The negative predictive value for VTE at 30 days was 96% and 93% in the derivation and validation cohorts, respectively, and the positive predictive value was 20% in both. We derived and validated a model using D-dimer and hemoglobin, which stratifies VTE risk in patients with ALL receiving asparaginase-based induction.

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Journal
Blood Advances
Published
2025-10-31
DOI
https://doi.org/10.1182/bloodadvances.2025017862
Primary Topic
Acute Lymphoblastic Leukemia research
Type
article
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article

Derivation and external validation of a venous thromboembolism risk prediction model in asparaginase-treated ALL

Guru Subramanian Guru Murthy, Ofir Wolach, Brian J. Carney, W Stock et al.
Blood Advances
Acute Lymphoblastic Leukemia research
article

Derivation and external validation of a venous thromboembolism risk prediction model in asparaginase-treated ALL

Guru Subramanian Guru Murthy, Ofir Wolach, Brian J. Carney, W Stock, Jeffrey I. Zwicker, Kristen Marie O’Dwyer, Renana Robinson, Daniela R. Anderson, Selina M. Luger, Radhika Gangaraju, Anjani Kapadia, Marlise Rachael Luskin, Tzu‐Fei Wang, Anke M. Gerrits, Kristen M. Sanfilippo, Avi Leader, Shai O. Shimony, Wafik G. Sedhom, Marc Carrier, Jill Fulcher, Hannah Levavi, Shira Naomi Dinner, Eva N. Hamulyák, Bart J. Biemond, Talha Badar, David Nemirovsky, Andriy Derkach, William E. Shomali, Mark Robert Litzow, Michaela Liedtke, Chandrasekar Muthiah, Grace Van Hyfte, Michal Bar‐Natan, Leah Goldberg, Karan Bansal
article en

Abstract

The incidence of venous thromboembolism (VTE) in patients with acute lymphoblastic leukemia (ALL) receiving asparaginase-based induction is high despite primary thromboprophylaxis. Our aim was to derive and externally validate a VTE risk prediction model in patients with ALL receiving asparaginase-based induction. We conducted a multicenter retrospective cohort study of patients (aged ≥18 years) with newly diagnosed ALL receiving asparaginase-based induction. The derivation and external validation cohorts included 306 and 94 patients, respectively. Primary outcome was VTE at any site. A cause-specific Cox proportional hazards model stratified by thromboprophylaxis and center was performed to identify VTE risk factors in the derivation cohort. A risk prediction model for VTE at 30 days was derived using variables with P value < .05 in the multivariable model and was tested in the validation cohort. VTE risk factors on multivariable analysis in the derivation cohort included D-dimer ≥1 μg fibrinogen equivalent unit per mL (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.07-6.5) and hemoglobin (HR for each 1 g/dL increment, 1.19; 95% CI, 1.06-1.34) at ALL diagnosis. A VTE risk score based on these variables distinguished between a 4% (95% CI, 0.72-12) and 20% (95% CI, 14-27) 30-day cumulative incidence of VTE in the derivation cohort, with similar findings in the validation cohort (area under the curve, 0.56). The negative predictive value for VTE at 30 days was 96% and 93% in the derivation and validation cohorts, respectively, and the positive predictive value was 20% in both. We derived and validated a model using D-dimer and hemoglobin, which stratifies VTE risk in patients with ALL receiving asparaginase-based induction.

Blood AdvancesVol. 10(3)
Northwestern University (US), Beth Israel Deaconess Medical Center (US), Mayo Clinic (US), Memorial Sloan Kettering Cancer Center (US), NewYork–Presbyterian Hospital (US), University of Ottawa (CA), Tel Aviv University (IL), Medical College of Wisconsin (US), Washington University in St. Louis (US), Cornell University (US), Tel Aviv Sourasky Medical Center (IL), Rabin Medical Center (IL), Ottawa Hospital (CA), Jacksonville College (US), WinnMed (US), University of Alabama at Birmingham (US), University of Chicago (US), University of Chicago Medical Center (US), Presbyterian Hospital (US), Stanford Health Care (US), OLVG (NL), Amsterdam Neuroscience (NL), Dana-Farber Cancer Institute (US), Tisch Hospital (US), Stanford Medicine (US), Mayo Clinic in Florida (US), Amsterdam University Medical Centers (NL), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, University of Rochester (US), Amsterdam University of Applied Sciences (NL), University of Pennsylvania (US), University of Amsterdam (NL), Stanford University (US), Icahn School of Medicine at Mount Sinai (US)
Amgen, Eli Lilly and Company, Pfizer, Sanofi, Gilead Sciences, Teva Pharmaceutical Industries, Alexion Pharmaceuticals, Celgene, Regeneron Pharmaceuticals, Jazz Pharmaceuticals, BeiGene, Incyte, Syndax Pharmaceuticals, Seagen, Novo Nordisk, Astellas Pharma, Servier, Swedish Orphan Biovitrum, MorphoSys, LEO Pharma, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, Daiichi Sankyo Europe
Openalex Percentile: Top 58%
Acute Lymphoblastic Leukemia research
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