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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