Table 5.

Operative algorithm based on patient age, BMI, and toxicities related to prior drug exposure used for the administration of Peg-ASP during chemotherapy courses no. 1, 2, 5, and 6 in GIMEMA trial LAL 2317 for adult Ph– ALL (age range 18–65 years; ClinicalTrials.gov identifier: NCT03367299). G denotes grade of toxicity according to the Common Toxicity Criteria scale.

Age group (years)	Cycle no.	Risk factorsa	Peg-ASP-related G3-4 toxicity observed at prior cycle/exposureb,c	Peg-ASP IU/m2 (max cumulative)
⩽55	1	No	–	1500 (3000)
		Yes	–	1000 (2000)
	2, 5, 6	No	No	2000 (3750)
			Yes	1000 (2000)
		Yes	No	1500 (3000)
			Yes	500 (1000)
>55	1	No	–	1000 (2000)
		Yes	–	500 (1000)
	2, 5, 6	No	No	1000 (2000)
			Yes	500 (1000)
		Yes	No	1000 (2000)
			Yes	No Peg-ASPd

^aPretreatment risk factors for Peg-ASP-related toxicity: hepatosteatosis (ultrasound scan), BMI >30.

^bHepatic, pancreatic, coagulation/thrombosis.

^cMust be reduced to less than G2 before next Peg-ASP dosing; G4 pancreatitis causes permanent Peg-ASP discontinuation.

^dIn subsequent cycle Peg-ASP will be restarted at a dose of 500 IU/m²; if G3-4 toxicity occurs again, PEG-ASP will be permanently discontinued.

ALL, acute lymphoblastic leukemia; BMI, body mass index; Peg-ASP, pegylated asparaginase; Ph–, Philadelphia chromosome-negative B-ALL.