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Safety, efficacy, and clinical utility of asparaginase in the treatment of adult patients with acute lymphoblastic leukemia

Authors Koprivnikar J, McCloskey J, Faderl S

Received 20 February 2016

Accepted for publication 6 July 2016

Published 6 March 2017 Volume 2017:10 Pages 1413—1422

DOI https://doi.org/10.2147/OTT.S106810

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Manfred Beleut

Peer reviewer comments 2

Editor who approved publication: Professor Min Li

Jamie Koprivnikar, James McCloskey, Stefan Faderl

Division of Leukemia, John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, NJ, USA

Abstract: Adults with acute lymphoblastic leukemia (ALL) are known to have inferior outcomes compared to the pediatric population. Although the reasons for this are likely manyfold, the agents utilized and the increased intensity of pediatric treatments compared to adult treatments are likely significant contributing factors. Asparaginase, an enzyme that converts asparagine to aspartic acid, forms the backbone of almost all pediatric regimens and works by depleting extracellular asparagine, which ALL cells are unable to synthesize. Asparaginase toxicities, which include hypersensitivity reactions, pancreatitis, liver dysfunction, and thrombosis, have hindered its widespread use in the adult population. Here, we review the toxicity and efficacy of asparaginase in adult patients with ALL. With the proper precautions, it is a safe and effective agent in the treatment of younger adults with ALL with response rates in the frontline setting ranging from 78% to 96%, compared to most trials showing a 4-year overall survival of 50% or better. The age cutoff for consideration of treatment with pediatric-inspired regimens is not clear, but recent studies show promise particularly in the adolescent and young adult population. New formulations of asparaginase are actively in development, including erythrocyte-encapsulated asparaginase, which is designed to minimize the toxicity and improve the delivery of the drug.

Keywords: PEG-asparaginase, ALL, chemotherapy, pegaspargase, AYA, pediatric
 

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