Asparaginase-associated toxicity in children with acute lymphoblastic leukemia

Figures & data

Table I. Asparaginase-associated toxicities and recommendations for management of asparaginase therapy [33,37–47].

Toxicity	Management of asparaginase therapy	References
Asparaginase hypersensitivityClinical hypersensitivitySubclinical hypersensitivity	Discontinue native E. coli–derived asparaginase or PEG-asparaginase in the case of hypersensitivity and switch patient to Erwinia asparaginaseIn the case of clinical hypersensitivity to an E. coli–derived asparaginase and Erwinia asparaginase, discontinue asparaginase therapyIn the case of subclinical hypersensitivity to an E. coli–derived asparaginase, switch patient to Erwinia asparaginase	Salzer et al. [33]Vrooman et al. [37]
Hyperglycemia	Asparaginase therapy should continue if patient shows normal glucose levels with insulin	Howard and Pui [38]
Pancreatitis	Discontinue asparaginase if amylase/lipase levels are ≥3 × ULN and/or imaging/clinical signs are compatible with pancreatitisMay rechallenge in patients with mild pancreatitis if within 48 hours the patient displays no symptoms, amylase/lipase levels <3 × ULN, and no pseudocysts or necrosis	Raja et al. [39]Stock et al. [40]*
Thrombosis	Withhold asparaginase in the case of clinically significant thrombosisRestart asparaginase under anticoagulation therapy once symptoms resolve	Payne and Vora [41]Truelove et al. [42]*Grace et al. [43]
Encephalopathy	Treat symptoms of encephalopathy and normalize serum ammonia levels if elevatedAsparaginase treatment may continue if symptoms are not life-threatening	Panis et al. [44]
Myelosuppression	Continue asparaginase treatmentReduce dose of other myelosuppressive agents (not recommended during induction)	Merryman et al. [45]
Hypertriglyceridemia	Maintain asparaginase therapy and monitor the patient closely for signs of pancreatitis	Tong et al. [46]Bhojwani et al. [47]
Hepatic toxicity	In adults, withhold asparaginase for clinical symptoms and alanine/glutamine aminotransferase >5.0–20.0 × ULNNo clear pediatric guidelines; asparaginase management varies across treatment protocols	Stock et al. [40]*

E. coli, Escherichia coli; PEG, pegylated; ULN, upper limit of normal.

*Focused on adult patients with acute lymphoblastic leukemia.

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Panis B, Vlaar AM, van Well GT, et al. Posterior reversible encephalopathy syndrome in paediatric leukaemia. Eur J Paediatr Neurol 2010; 14: 539–545.

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Merryman R, Stevenson KE, Gostic WJ, 2nd, et al. Asparaginase-associated myelosuppression and effects on dosing of other chemotherapeutic agents in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2012; 59: 925–927.

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Tong WH, Pieters R, de Groot-Kruseman HA, et al. Toxicity of very prolonged PEGasparaginase and Erwinia asparaginase courses in relation to asparaginase activity levels with a special focus on dyslipidemia. Haematologica 2014; 99: 1716–1721.

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