Table 2.
Recommended management of common asparaginase toxicities
| Toxicity | Grade 2 | Grade 3 | Grade 4 |
|---|---|---|---|
| Non-CNS thrombosis | Continue unless clinical signs or symptoms present | Withhold therapy until acute toxicity resolved and patient stabilized on anticoagulation | Withhold therapy until acute toxicity resolved and patient stabilized on anticoagulation |
| Non-CNS hemorrhage | Withhold therapy until bleeding is ≤ grade 1; do not withhold for hypofibrinogenemia in the absence of clinical findings | Withhold therapy until bleeding is ≤ grade 1 and factor replacement therapy is completed | Withhold therapy until bleeding is ≤ grade 1 and factor replacement therapy is completed |
| CNS thrombosis | Continue therapy assuming no clinical signs or symptoms (abnormal laboratory findings only) | Discontinue therapy until full resolution; may resume ASNase therapy at decreased dose or increased dosing interval | Permanent discontinuation of therapy |
| CNS hemorrhage | Continue therapy assuming no clinical signs or symptoms (abnormal laboratory findings only) | Discontinue therapy until full resolution; may resume ASNase therapy at decreased dose or increased dosing interval | Permanent discontinuation of therapy |
| Hepatic transaminitis | Continue as long as elevations remain < 3–5 times the ULN | For elevation >5–20 times the ULN, delay dose until < grade 2 | For elevation >20 times the ULN, discontinue if toxicity reduction to < grade 2 takes longer than 1 week |
| Hyperbilirubinemia | Continue if direct bilirubin is <3.0 mg/dL | If direct bilirubin is 3.1–5.0 mg/dL, hold until direct bilirubin is <2.0 mg/dL | If direct bilirubin is >5.0 mg/dL, discontinue. Do not make up for missed doses |
| Hypertriglyceridemia | If serum triglycerides <1,000 mg/dL, monitor closely for development of pancreatitis | If triglycerides >1,000 mg/dL, hold therapy and resume at a lower dose when triglycerides are at baseline | If triglycerides >1,000 mg/dL, hold therapy and resume at a lower dose when triglycerides are at baseline |
| Pancreatitis | Continue for asymptomatic elevations in amylase and lipase <3 times the ULN or only for radiologic findings | Hold therapy for elevations in amylase or lipase >3 times the ULN until stabilized or declining | Permanently discontinue for clinical pancreatitis |
| Hypersensitivity | Continue for urticaria without bronchospasm, hypotension, or edema | For bronchospasm, angioedema, or hypotension, discontinue. If Erwinia asparaginase is available, replace PEG-asparaginase dose with 6 doses of Erwinia asparaginase 25,000 IU/m2 IM every other day | For life-threatening reactions, discontinue. If Erwinia asparaginase available, replace PEG-asparaginase dose with 6 doses of Erwinia asparaginase 25,000 IU/m2 IM every other day |
Abbreviations: ASNase, asparaginase; CNS, central nervous system; IM, intramuscular; ULN, upper limit of normal; PEG, polyethylene glycol.