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

Abstract

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.