Haematologica
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Haematologica, Vol 91, Issue 1, 24-31
Copyright © 2006 by Ferrata Storti Foundation

Clinical Trial

A pharmacological study on pegylated asparaginase used in front-line treatment of children with acute lymphoblastic leukemia

C Rizzari, M Citterio, M Zucchetti, V Conter, R Chiesa, A Colombini, S Malguzzi, D Silvestri, and M D'Incalci

Department of Pediatric Hematology-Oncology, University of Milano-Bicocca, S. Gerardo Hospital, Monza, Italy. carmelo.rizzari@pediatriamonza.it

BACKGROUND AND OBJECTIVES: Pegylated-asparaginase (PEG-ASP) has been traditionally used as a second-line preparation in children with acute lymphoblastic leukemia (ALL) presenting with clinical allergy to native asparaginase (ASP) products. The main goal of the present study was to investigate the pharmacological effects of the administration of PEG-ASP given as a first-line product in children with ALL. DESIGN AND METHODS: PEG-ASP serum enzymatic activity and serum and cerebrospinal fluid (CSF) levels of asparagine were investigated in 20 children with newly diagnosed ALL enrolled in the ongoing AIEOP ALL 2000 protocol and treated with PEG-ASP as a first-line ASP preparation. During induction the drug was administered at the dosage of 1,000 U/m2 i.v. on days 12 and 27. During reinduction the drug was administered only once at the same dosage. RESULTS: Among the 20 patients treated in induction serum PEG-ASP activity equalled or exceeded 100 U/L in 18/18, 11/11 and 15/18 of the samples available on days 22, 25 and 27, respectively, and in 16/16, 12/15 and 5/8 samples available on days 36, 39 and 45, respectively. In the 15 patients treated during reinduction serum PEG-ASP activity > or =100 U/L was observed in 14/15, 11/14, 6/10, and 0/12 samples available on days 11, 15, 18 and 23, respectively, after the administration of the drug. Serum asparagine levels were below the detection limit (< or =0.2 microM) in all patients/samples and at all time points evaluated during induction; during reinduction only one patient had detectable asparagine levels from day 11. CSF asparagine levels were below the detection limit of the method only in a few patients during both induction and reinduction. INTERPRETATION AND CONCLUSIONS: PEG-ASP given as a first-line ASP product in the context of an intensive chemotherapy protocol for pediatric ALL allowed adequate plasma enzymatic activity and asparagine depletion during both exposures to the drug. However, CSF asparagine depletion was inadequate.


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