Venous Thromboembolism Risk in AYAs with ALL on Pediatric-Inspired Regimens
Overview
In a cohort of 341 adolescent and young adult (AYA) patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric-inspired regimens, 33.4% experienced venous thromboembolism (VTE). Elevated BMI and absence of hyperdiploid karyotype were associated with increased VTE risk, while prophylactic low molecular weight heparin (LMWH) reduced VTE incidence in a subset of patients.
Background
Pediatric-inspired chemotherapy regimens incorporating asparaginase (ASP) are effective in treating AYAs with ALL but carry a risk of venous thromboembolism (VTE) due to decreased synthesis of anticoagulant proteins. Reported VTE rates in this population range widely from 5% to 34%, with events most commonly occurring during induction therapy. Risk factors such as older age and lymphadenopathy have been identified, but the impact of prophylactic anticoagulation and the long-term clinical consequences of VTE remain unclear. This study retrospectively evaluated VTE prevalence, risk factors, and outcomes in AYAs treated on Dana-Farber Cancer Institute (DFCI) ALL Consortium protocols.
Data Highlights
Characteristic
VTE (n=114)
No VTE (n=227)
p-value
Median Age (years)
23.2 (IQR 17.2–33.3)
23.2 (IQR 17.2–33.3)
NS
Male, n (%)
62.2%
62.2%
NS
Elevated BMI (overweight/obese)
50.9%
39.6%
0.048
Hyperdiploid karyotype, n (%)
3.5%
13.2%
0.0038
Treated on trial per protocol, n (%)
29.8%
20.3%
0.049
Median follow-up (years)
3.8 (range 0–16)
3.8 (range 0–16)
NS
Key Findings
One-third (33.4%) of AYAs with ALL experienced at least one VTE event during treatment with ASP-containing pediatric-inspired regimens.
Elevated BMI (overweight/obese) was significantly associated with increased VTE risk (50.9% vs. 39.6%, p=0.048).
Patients with hyperdiploid karyotype had a lower incidence of VTE (3.5% vs. 13.2%, p=0.0038).
Implementation of LMWH thromboprophylaxis after September 2011 in the 06-254 protocol reduced VTE incidence in patients receiving ASP.
VTE events did not lead to discontinuation of ASP or removal from treatment protocols; therapeutic anticoagulation was initiated upon VTE diagnosis.
Risk factors such as older age and lymphadenopathy were previously reported but not detailed in this cohort’s key findings.
Clinical Implications
Clinicians should recognize that AYAs with ALL undergoing ASP-containing pediatric-inspired regimens are at substantial risk for VTE, particularly those with elevated BMI and non-hyperdiploid karyotypes. Prophylactic anticoagulation with LMWH during ASP treatment may reduce VTE incidence without necessitating interruption of chemotherapy. Close monitoring and early intervention for VTE can optimize treatment continuity and patient outcomes.
Conclusion
VTE is a common and clinically significant complication in AYAs treated with pediatric-inspired ALL regimens incorporating asparaginase. Prophylactic strategies such as LMWH thromboprophylaxis appear beneficial in reducing VTE risk and supporting uninterrupted therapy.
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
