Asparaginase Adverse Events in AYA ALL: Hepatotoxicity, Thrombosis, and Pancreatitis

Dr. Silverman introduces the Haematologica expert consensus published by Dr. Curran and colleagues in December 2025, describing it as the most comprehensive adult-focused guidance available on recognizing and managing asparaginase-associated adverse events. Dr. Curran summarizes the major clinically significant adverse events encountered with asparaginase therapy in adults and AYAs: hypersensitivity (more common in pediatric populations), hepatotoxicity, thrombosis, and pancreatitis. She identifies hepatotoxicity and thrombosis as the adverse events most likely to drive premature and unnecessary discontinuation in adult practice.

Regarding hepatotoxicity: liver function tests (LFTs) can rise significantly with asparaginase therapy, but this elevation does not cause long-term hepatic damage in the vast majority of cases. The consensus reviews strategies to mitigate and resolve LFT elevations, and emphasizes clearly that markedly elevated LFTs alone are not a definitive indication to permanently discontinue asparaginase. Regarding thrombosis: asparaginase-associated thrombosis is a manageable toxicity with standard anticoagulation; patients who develop venous thromboembolism on asparaginase can safely continue therapy with anticoagulation on board, and age is the primary identified risk factor for thrombosis risk. Antithrombin III (AT3) repletion, although historically practiced in pediatrics, has not been definitively shown to prevent thrombosis, and data remain confusing.

Regarding pancreatitis: clinically significant pancreatitis (not merely asymptomatic lipase or amylase elevation) is generally regarded as a contraindication to asparaginase rechallenge in adults, given high recurrence rates. The consensus provides a framework for distinguishing laboratory-only findings from clinical pancreatitis to guide management decisions.