Incidence and Predictors of Symptomatic Thrombosis During Asparaginase-containing Therapy in Children With Acute Lymphoblastic Leukemia: A Meta-analysis and Narrative Synthesis.

OBJECTIVES

Symptomatic thrombosis is a clinically important complication of asparaginase-containing therapy in children with acute lymphoblastic leukemia (ALL), but reported incidence and predictors vary across studies. We conducted a systematic review and meta-analysis to estimate its incidence and synthesize reported predictors.

METHODS

PubMed, Embase, Web of Science Core Collection, Scopus, and the Cochrane Library were searched from inception through April 15, 2026. Eligible studies enrolled patients aged ≤21 years with ALL receiving asparaginase-containing therapy and reported extractable incidence or predictor data for overall symptomatic thrombosis or symptomatic venous thromboembolism. Proportions were pooled after logit transformation using a random-effects model. Predictor data were synthesized narratively when quantitative pooling was inappropriate.

RESULTS

Twenty-three studies met the eligibility criteria; 15 studies involving 17,809 children and 655 events contributed to the incidence meta-analysis. The pooled incidence of symptomatic thrombosis was 5.6% (95% CI: 3.5%-9.0%), with substantial heterogeneity (I²=96.9%). Study-specific estimates ranged from ∼1% to 22.7%. Older age was the most consistently reported predictor; associations with inherited thrombophilia, non-O blood group, high-risk treatment status, and T-ALL phenotype were inconsistent across cohorts.

CONCLUSIONS

Symptomatic thrombosis affects ∼6% of children with ALL receiving asparaginase-containing therapy, although incidence varies considerably across studies. Older age was the most reproducible risk factor, whereas evidence for other predictors remains heterogeneous.