Clinical Scorecard: Venous Thromboembolism Risk in Adolescents and Young Adults with Acute Lymphoblastic Leukemia Undergoing Pediatric-Inspired Treatment Regimens
At a Glance
Category
Detail
Condition
Acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA)
Key Mechanisms
Asparaginase-induced depletion of anticoagulant proteins (plasminogen, antithrombin, protein C, protein S) leading to increased venous thromboembolism (VTE) risk
Target Population
AYA patients aged 15–50 years with Philadelphia chromosome-negative ALL
Care Setting
Multi-center oncology protocols including Dana-Farber Cancer Institute Consortium and affiliated hospitals
Key Highlights
VTE incidence in AYAs treated with asparaginase-containing regimens ranges from 5% to 34%, most commonly during induction phase.
Risk factors for VTE include older age, lymphadenopathy, and elevated BMI (overweight/obese).
Implementation of low molecular weight heparin (LMWH) prophylaxis and antithrombin repletion reduced VTE incidence in high-risk protocols.
Guideline-Based Recommendations
Diagnosis
Monitor for VTE events especially during induction and consolidation phases of ASP treatment.
Use clinical and imaging assessments to confirm VTE diagnosis.
Management
Initiate therapeutic anticoagulation promptly upon VTE diagnosis without discontinuing asparaginase therapy or protocol participation.
Administer LMWH thromboprophylaxis during ASP treatment in high-risk protocols.
Provide antithrombin repletion if activity levels fall below 30%.
Monitoring & Follow-up
Regularly assess anticoagulant protein levels during ASP therapy.
Monitor body mass index and other risk factors to identify patients at increased VTE risk.
Track VTE incidence and adjust prophylaxis protocols accordingly.
Risks
Increased VTE risk associated with asparaginase-induced anticoagulant protein depletion.
Potential complications from VTE including morbidity and impact on survival.
Confounding effects of ASP exposure on survival outcomes.
Patient & Prescribing Data
AYA patients aged 15–50 years with Philadelphia chromosome-negative ALL treated on DFCI Consortium protocols
Use of pegylated or non-pegylated asparaginase with continuous exposure during consolidation; LMWH prophylaxis introduced in later protocols after high VTE incidence observed; therapeutic anticoagulation used after VTE diagnosis without stopping ASP.
Clinical Best Practices
Incorporate LMWH prophylaxis during ASP treatment in patients at high risk for VTE.
Maintain ASP therapy despite VTE occurrence to preserve treatment efficacy.
Use antithrombin supplementation to maintain activity levels above 30% during ASP therapy.
Perform landmark survival analyses to account for confounding effects of ASP exposure on outcomes.
Classify BMI using age-adjusted percentiles for patients under 20 and absolute BMI for those 20 and older to stratify VTE risk.
by Shai Shimony, Hari S. Raman, Yael Flamand, Julia Keating, Jonathan D. Paolino, Yannis K. Valtis, Andrew E. Place, Lewis B. Silverman, Stephen E. Sallan, Lynda M. Vrooman, Andrew M. Brunner, Donna S. Neuberg, Ilene Galinsky, Jacqueline S. Garcia, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Jean M. Connors, Daniel J. DeAngelo, Marlise R. Luskin
