Table 1 Statements and results of the Delphi consensus process

 1.1

Peg-ASP is a pivotal medication in the treatment of ALL, indispensable if the treatment aim is curative

100% affirmative

 1.2

There are patients for whom there is an absolute contraindication to the use of Peg-ASP (age, comorbidity)

Consensus not reached

 1.3

The study of patient-associated risk factors may significantly limit the incidence of adverse events related to the use of Peg-ASP

100% affirmative

 1.4

The toxicities associated with the administration of Peg-ASP are manageable in the majority of adult patients

100% affirmative

 2.1

It is difficult to predict and characterize by significant variability from patient to patient (individual predisposition

Consensus not reached

 2.2

Appropriate knowledge is needed of the mechanisms underlying the development of toxicities in order to establish adequate preventive measures and early intervention at the onset of toxicity

100% affirmative

 2.3

It may potentially be influenced by concomitant therapies (chemotherapy, antibiotics, antifungals, steroids)

95% affirmative

 2.4

Fatal outcome on rare occasions

100% affirmative

 3.1

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

74% affirmative

 3.2

In case of known grade 3–4 allergic reaction, further administrations of Peg-ASP are contraindicated

95% affirmative

 3.3

In case of established grade 3–4 allergic reaction to Peg-ASP, substitution with the Erwinia chrysanthemi formulation is indicated

95% affirmative

 3.4

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

74% affirmative

 4.1

It is the most frequent toxicity and therefore requires close monitoring (pre-during-post-therapy)

95% affirmative

 4.2

In addition to abdominal ultrasound, other instrumental examinations are recommended prior to initiating Peg-ASP therapy

Consensus not reached

 4.3

BMI > 30 and pre-existing hepatic steatosis contraindicate the use of Peg-ASP

89% negative

 4.4

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

89% affirmative

 4.5

Regardless of severity and degree of compensation, a diagnosis of chronic liver disease is an absolute contraindication of Peg-ASP treatment

74% negative

 4.6

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

68% affirmative

 5.1

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

95% affirmative

 5.2

L-carnitine is recommended in the event of hyperbilirubinemia

89% affirmative

 5.3

Hyperglycaemia should only be corrected with insulin therapy

84% affirmative

 5.4

Hypoalbuminemia should be corrected

95% affirmative

 6.1

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

100% affirmative

 6.2

The use of fresh plasma to correct hypofibrinogenemia is not recommended in the absence of haemorrhagic symptoms

89% affirmative

 6.3

Prophylaxis with LMWH is always recommended

consensus not reached

 6.4

Any concomitant oral contraceptives or hormone replacement therapy should be discontinued

95% affirmative

 6.5

It is advisable to correct hypofibrinogenemia with cryoprecipitate

79% affirmative

 6.6

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

100% affirmative

 7.1

Therapy should be discontinued if asymptomatic pancreatitis develops (CTCAE grade 2, i.e. enzymes > 3 times normal or radiological evidence)

Consensus not reached

 7.2

The dosage should be reduced if asymptomatic pancreatitis develops (CTCAE grade 2, i.e. enzymes > 3 times normal or radiological evidence)

Consensus not reached

 7.3

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

95% affirmative

 7.4

Development of CTCAE grade 2 pancreatitis contraindicates subsequent administrations even with a different ASP formulation (Erwinia chrysanthemi)

79% negative

 7.5

Development of CTCAE grade 3–4 pancreatitis contraindicates subsequent administrations even with a different ASP formulation (Erwinia chrysanthemi)

95% affirmative

 8.1

In the event of hyperglycemia with Peg-ASP and steroid therapy, it may be appropriate to reduce the steroid dose and enhance the insulin therapy rather than delay subsequent administrations of Peg-ASP

100% affirmative

 8.2

Patients being treated should be monitored for triglycerides

100% affirmative

 8.3

In case of severe (> 500 mg/dl), persistent, isolated hypertriglyceridemia, it is advisable to delay subsequent administrations of ASP

Consensus not reached

 8.4

There is insufficient evidence that reducing the Peg-ASP dose reduces development of hepatopancreatic, thrombotic and metabolic toxicity

Consensus not reached

 8.5

A preventive reduction in the dosage is always advisable if factors predisposing the development of toxicity are identified (e.g. BMI > 30, hepatosteatosis)

84% affirmative consensus

 9.1

Monitoring of asparaginase plasmatic activity is essential in clinical practice in order to optimize the therapeutic activity of asparaginase (e.g. change of formulation in case of drug inactivation)

74% affirmative

 9.2

In clinical practice, routine monitoring of ASP plasmatic activity is useful in all patients with ALL

Consensus not reached

 9.3

Searching for anti-asparaginase antibodies is of questionable value and should not therefore be routinely performed outside research studies in adult ALL

74% affirmative