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® (n = 15), or E. coli medac® (n = 47) L-ASE products, given either i.m. or i.v., at the standard dosage of 10,000 IU/m², 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® was however significantly higher when compared with that of Erwinase®. Conclusions: L-ASN depletion after a first exposure to standard doses of Erwinase® or medac® is obtained in virtually all patients. No differences are seen between the I.M. or I.V. administration routes but the medac® product is associated with a significantly higher enzyme activity in respect of Erwinase®. 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.