L-asparaginase in the treatment of patients with acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that predominantly occurs in children between 2 and 10 years of age. L-asparaginase is an integral component of treatment for patients with ALL and since its introduction into pediatric treatment protocols in the 1960s, survival rates in...

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Main Authors:	Egler, Rachel A., Ahuja, Sanjay P., Matloub, Yousif
Format:	Online
Language:	English
Published:	Medknow Publications & Media Pvt Ltd 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936081/

id	pubmed-4936081
recordtype	oai_dc
spelling	pubmed-49360812016-07-20 L-asparaginase in the treatment of patients with acute lymphoblastic leukemia Egler, Rachel A. Ahuja, Sanjay P. Matloub, Yousif Review Article Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that predominantly occurs in children between 2 and 10 years of age. L-asparaginase is an integral component of treatment for patients with ALL and since its introduction into pediatric treatment protocols in the 1960s, survival rates in children have progressively risen to nearly 90%. Outcomes for adolescent and young adult (AYA) patients, aged 15-39 years and diagnosed with ALL, have historically been less favorable. However, recent reports suggest substantially increased survival in AYA patients treated on pediatric-inspired protocols that include a greater cumulative dose of asparaginase. All currently available asparaginases share the same mechanism of action - the deamination and depletion of serum asparagine levels - yet each displays a markedly different pharmacokinetic profile. Pegylated asparaginase derived from the bacterium Escherichia coli is used as first-line therapy; however, up to 30% of patients develop a treatment-limiting hypersensitivity reaction. Patients who experience a hypersensitivity reaction to an E. coli-derived asparaginase can continue treatment with Erwinia chrysanthemi asparaginase. Erwinia asparaginase is immunologically distinct from E. coli-derived asparaginases and exhibits no cross-reactivity. Studies have shown that with adequate dosing, therapeutic levels of Erwinia asparaginase activity can be achieved, and patients switched to Erwinia asparaginase due to hypersensitivity can obtain outcomes similar to patients who do not experience a hypersensitivity reaction. Therapeutic drug monitoring may be required to ensure that therapeutic levels of asparaginase activity are maintained. Medknow Publications & Media Pvt Ltd 2016 /pmc/articles/PMC4936081/ /pubmed/27440950 http://dx.doi.org/10.4103/0976-500X.184769 Text en Copyright: © Journal of Pharmacology and Pharmacotherapeutics http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Egler, Rachel A. Ahuja, Sanjay P. Matloub, Yousif
spellingShingle	Egler, Rachel A. Ahuja, Sanjay P. Matloub, Yousif L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
author_facet	Egler, Rachel A. Ahuja, Sanjay P. Matloub, Yousif
author_sort	Egler, Rachel A.
title	L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
title_short	L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
title_full	L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
title_fullStr	L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
title_full_unstemmed	L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
title_sort	l-asparaginase in the treatment of patients with acute lymphoblastic leukemia
description	Acute lymphoblastic leukemia (ALL) is a hematologic malignancy that predominantly occurs in children between 2 and 10 years of age. L-asparaginase is an integral component of treatment for patients with ALL and since its introduction into pediatric treatment protocols in the 1960s, survival rates in children have progressively risen to nearly 90%. Outcomes for adolescent and young adult (AYA) patients, aged 15-39 years and diagnosed with ALL, have historically been less favorable. However, recent reports suggest substantially increased survival in AYA patients treated on pediatric-inspired protocols that include a greater cumulative dose of asparaginase. All currently available asparaginases share the same mechanism of action - the deamination and depletion of serum asparagine levels - yet each displays a markedly different pharmacokinetic profile. Pegylated asparaginase derived from the bacterium Escherichia coli is used as first-line therapy; however, up to 30% of patients develop a treatment-limiting hypersensitivity reaction. Patients who experience a hypersensitivity reaction to an E. coli-derived asparaginase can continue treatment with Erwinia chrysanthemi asparaginase. Erwinia asparaginase is immunologically distinct from E. coli-derived asparaginases and exhibits no cross-reactivity. Studies have shown that with adequate dosing, therapeutic levels of Erwinia asparaginase activity can be achieved, and patients switched to Erwinia asparaginase due to hypersensitivity can obtain outcomes similar to patients who do not experience a hypersensitivity reaction. Therapeutic drug monitoring may be required to ensure that therapeutic levels of asparaginase activity are maintained.
publisher	Medknow Publications & Media Pvt Ltd
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4936081/
_version_	1613605426305171456

L-asparaginase in the treatment of patients with acute lymphoblastic leukemia

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