Cerebral sinovenous thrombosis and asparaginase re‐exposure in patients aged 1–45 years with acute lymphoblastic leukaemia: A NOPHO ALL2008 study

Abstract

Abstract Cerebral sinovenous thrombosis (CSVT) is a serious complication during asparaginase therapy in patients with acute lymphoblastic leukaemia (ALL). We identified 46 patients with CSVT among 2651 patients (1‒45 years) treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol between 2008 and 2018. CSVT cases were prospectively registered in the NOPHO database with retrospective updates. We examined the frequency of asparaginase re‐exposure after CSVT, potential factors associated with asparaginase truncation, and sequelae after CSVT. This work was supported by the Danish Cancer Society and the Danish Childhood Cancer Foundation. The 2.5‐year cumulative incidence of CSVT was 1.9% (95% confidence interval 1.4%–2.5%). The majority of patients (74%, n = 31) were re‐exposed to asparaginase (with low‐molecular‐weight heparin coverage), one of whom had a second CSVT, without neurological sequelae. Patients re‐exposed to asparaginase were earlier in ALL treatment and lacked more asparaginase doses than non‐re‐exposed patients at CSVT diagnosis (median 50 vs. 81 days, p = 0.03; mean 11.2 vs. 8.4 asparaginase doses, p = 0.04). No other examined factors had an impact on asparaginase re‐exposure. At the last follow‐up (median 4.5 years after CSVT), 61% of patients had normal neurological status, and 57% had complete recanalisation of CSVT, with no significant difference between patients re‐exposed and non‐re‐exposed to asparaginase. Our results indicate that re‐exposure to asparaginase is safe after CSVT during anticoagulation.

Keywords

• acute leukaemia
• chemotherapy
• childhood leukaemia
• late effects of therapy
• thrombosis