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Table 2 Summary of the main advices from Delphi questionnaire in the management of Peg-ASP toxicity

From: National Italian Delphi panel consensus: which measures are indicated to minimize pegylated-asparaginase associated toxicity during treatment of adult acute lymphoblastic leukemia?

No

Prevention and Management

1. Hypersensitivity reactions

 

It is advisable to pre-medicate every administration of Peg-ASP to reduce incidence and/or severity of hypersensitivity reactions

In case of known grade 3–4 allergic reaction, further administrations of Peg-ASP are contraindicated and substitution with the Erwinia chrysanthemi formulation is indicated

In case of a clinically manifested hypersensitivity reaction, ASP activity should be measured to promptly identify any possible inactivation of the medication

2. Hepatic toxicity

 

BMI > 30 and pre-existing hepatic steatosis require a reduction in the dosage of Peg-ASP

Development of grade 3–4 toxicity does not contraindicate subsequent administrations of Peg-ASP when grade toxicity ≤2

L-carnitine is suggested in the event of hyperbilirubinemia

Concomitant therapy (chemotherapy, antibiotics, antifungals, steroids, other) plays a decisive role in increasing the risk of hepatotoxicity during Peg-ASP therapy

3. Metabolic toxicity

 

Hyperglycaemia should be corrected with insulin therapy and it is not an indication to discontinue or delay subsequent PegAsp administrations

Hypoalbuminemia should be corrected

4. Hemorrhagic/thrombotic toxicity

 

Laboratory alterations of the hemocoagulative parameters in the absence of clinical signs of thrombosis or bleeding do not necessitate discontinuation or delay of Peg-ASP

It is advisable to correct hypofibrinogenemia with cryoprecipitate

Replenishment of AT is advisable to maintain levels consistently above 60%

5. Peg asparaginase-associated pancreatitis

 

CTCAE grade 2 asymptomatic pancreatitis, once resolved, does not contraindicate subsequent administration of Peg-ASP

Development of symptomatic pancreatitis or asymptomatic with CTCAE grade 3–4 amylase/lipase elevation contraindicates subsequent administrations even with a different ASP formulation