Thrombosis-Associated Risk Factors in Pediatrics and Adults Treated with Asparaginase-Containing Chemotherapy for ALL: A Systematic Review and Meta-Analysis

Background: Thromboembolism is a serious complication in acute lymphoblastic leukemia (ALL). This systematic review and meta-analysis evaluated thrombosis incidence and risk factors across populations receiving asparaginase-based therapy. Methods: From 214 studies (1994–2026), 58 met inclusion criteria, totaling 23,655 adult, pediatric, and mixed-population patients. Searches included Ovid MEDLINE, Embase, Cochrane CENTRAL, PubMed Central, and Google Scholar. Eligible studies were observational cohorts or clinical trials reporting thrombosis in ALL patients treated with asparaginase. Risk factors assessed included study design, asparaginase formulation, immunophenotype, gender, treatment phase, corticosteroid use, mediastinal mass, ABO blood group, body weight, and age. Random-effects models were used for meta-analysis, and risk of bias was assessed using ROBINS-I and RoB-2. Results: Adults had significantly higher thrombosis rates than children (p < 0.0001). Study design, asparaginase formulation, immunophenotype, and treatment phase differed significantly across age groups (p < 0.0001). T-cell ALL showed higher thrombosis rates than B-cell ALL (p < 0.0001). Significant pediatric risk factors included age ≥ 10 years, mediastinal mass, non-O blood type, and overweight/obesity (all p ≤ 0.0004). Gender and corticosteroid use were not significant predictors. Findings were limited by substantial heterogeneity across included studies. Conclusions: Thrombosis risk was multifactorial. Adults and older children had higher risk, and pediatric patients with overweight/obesity, mediastinal mass, or non-O blood type were particularly vulnerable. Thromboprophylaxis is advised for high-risk groups. This review was not registered and received no external funding.