Symptomatic Cerebral Sinovenous Thrombosis Associated With L-Asparaginase In Children With Acute Lymphoblastic Leukemia: A Single Institution Experience Over 17 Years.

BACKGROUND

Cerebral sinovenous thrombosis (CSVT) is a rare, yet important complication of acute lymphoblastic leukemia (ALL) therapy, associated with significant morbidity and mortality. Paucity of data from India prompted us to report our experience with CSVT over a period of 17 years.

MATERIALS AND METHODS

This is a retrospective analysis of 500 consecutive ALL patients, below 18 year of age, treated between January 1998 and December 2014, who developed symptomatic CVST.

RESULTS

Seven of the 467 eligible patients developed symptomatic CVST with an incidence of 1.5% (7/467). Six of the CVST events, occurred during induction and 1 during reinduction. Median time to symptoms was 21 days (range, 2 to 27 d) from first exposure to L-asparaginase therapy. Management included low-molecular-weight heparin (enoxaparin sodium) at a dose of 1 mg/kg twice a day for at least 3 months along with supportive care. There were 2 thrombosis-attributable deaths. The remaining patients tolerated rechallenge with L-asparaginase uneventfully during reinduction, under cover of heparin prophylaxis. Complete neurological recovery was observed in all surviving patients.

CONCLUSIONS

Incidence of symptomatic L-asparaginase associated CSVT during ALL treatment was 1.5% with high case fatality rate (28%). It is noteworthy that full neurological recovery is likely in surviving patients, and rechallenge with L-asparaginase is safe with heparin prophylaxis. Currently available screening methods are not practically implementable in resource-limited settings.