L-asparagine depletion and L-asparaginase activity in children with acute lymphoblastic leukemia receiving i.m. or i.v. Erwinia C. or E-coli L-asparaginase as first exposure

Purpose: The present study was aimed at investigating L-asparaginase (L-ASE) activity (in plasma) and L-asparagine (L-ASN) depletion (in plasma and CSF) in children with newly diagnosed acute lymphoblastic leukemia (ALL) exposed for the first time to different L-ASE products. Patients and methods: During the induction treatment of the AIEOP ALL 95 study, 62 patients were treated with either Erwinase(R) (n = 15), or E. coli medac(R) (n = 47) L-ASE products, given either i.m. or i.v., at the standard dosage of 10,000 IU/m(2), q 3 days x 8 (first exposure). Results: Plasma and CSF L-ASN trough levels were undetectable in all cases, including those with L-ASE trough activity < 50 mU/ml. L-ASE trough activity during the administration of medac(R) was however significantly higher when compared with that of Erwinase(R). Conclusions: L-ASN depletion after a first exposure to standard doses of Erwinase(R) or medac(R) is obtained in virtually all patients. No differences are seen between the I.M. or I.V. administration routes but the medac(R) product is associated with a significantly higher enzyme activity in respect of Erwinase(R). L-ASN levels may be undetectable also in patients with L-ASE trough activity levels < 50 mU/ml, challenging the current opinion that an activity level of 100 mU/ml is needed to obtain L-ASN depletion.