Cerebrovascular thrombosis during pediatric ALL therapy: a case series highlighting temporal association with PEG-asparaginase exposure.

BACKGROUND

Cerebrovascular thrombosis is an uncommon but potentially life-threatening complication of chemotherapy in children with acute lymphoblastic leukemia (ALL). Although PEG-asparaginase-associated thrombosis has been widely recognized, the temporal pattern, laboratory evolution, and management characteristics of cerebrovascular events remain incompletely described.

METHODS

We conducted a retrospective single-center case series of pediatric patients with acute lymphoblastic leukemia (ALL) treated between January 2018 and December 2025. Clinical records, serial coagulation parameters, neuroimaging findings, treatment strategies, and outcomes of patients who experienced cerebrovascular thrombotic events during chemotherapy were reviewed descriptively.

RESULTS

Among 1,138 pediatric patients with ALL treated during the study period, six developed radiologically confirmed cerebrovascular thrombosis (incidence proportion, 0.53%; median age, 10 years). Five patients developed cerebral venous sinus thrombosis (CVST) and one developed acute ischemic stroke (AIS). Five of six events in this small cohort occurred within 5-17 days after PEG-asparaginase administration. At symptom onset, all patients exhibited markedly elevated D-dimer levels and reduced antithrombin III (AT-III) activity. Following treatment, D-dimer levels declined within 1-3 days, whereas AT-III activity recovered more gradually over 5-13 days. Four patients with CVST received therapeutic low-molecular-weight heparin and achieved favorable neurological outcomes. One patient with AIS underwent successful mechanical thrombectomy with substantial neurological improvement. No recurrent thrombotic events were observed during follow-up.

CONCLUSIONS

In this case series, cerebrovascular thrombosis during pediatric ALL therapy showed a distinct temporal clustering pattern within 5-17 days after PEG-asparaginase exposure and was consistently associated with reduced AT-III activity and elevated D-dimer levels. These findings suggest a potential high-risk period during which focused coagulation monitoring may facilitate earlier diagnosis and timely therapeutic intervention.