Cited by 334Acute Lymphoblastic Leukemia researchDrug-Induced Adverse ReactionsChronic Lymphocytic Leukemia Research

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

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Egler, Rachel A., Ahuja, Sanjay P., Matloub, Yousif·2016·Journal of Pharmacology and Pharmacotherapeutics

DOI 10.4103/0976-500x.184769PMC PMC4936081

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Abstract

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.

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Authors: Egler, R. A., Ahuja, S. P., & Matloub, Y.
Affiliations: Rainbow Babies & Children's Hospital (US)
Corresponding author: Egler, Rachel A.
ORCID: Ahuja, Sanjay P.
Venue: Journal of Pharmacology and Pharmacotherapeutics
Publisher: SAGE Publications
Published: 2016-06
Volume: 7
Issue: 2
Pages: 62-71
ISSN: 0976-500X (ISSN-L)
0976-5018
DOI: 10.4103/0976-500x.184769
PMC: PMC4936081
OpenAlex: W2471256249
Cited by: 334
References: 99
Citations by year: 2026: 24 · 2025: 28 · 2024: 42 · 2023: 50 · 2022: 36 · 2021: 55 · 2020: 37 · 2019: 26 · 2018: 17 · 2017: 17 · 2016: 1
FWCI: 20.16
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/3.0/ (unspecified)
Locations: Journal of Pharmacology and Pharmacotherapeutics (publishedVersion, cc-by-nc-sa)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion, cc-by-nc-sa)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Acute Lymphoblastic Leukemia research
Health Sciences › Medicine › Pharmacology (medical) › Drug-Induced Adverse Reactions
Health Sciences › Medicine › Hematology › Chronic Lymphocytic Leukemia Research
Keywords: L-asparaginase, acute lymphoblastic leukemia, childhood acute lymphoblastic leukemia, adolescent and young adult leukemia, pegylated asparaginase, hypersensitivity, cross-reactivity, pharmacokinetics, therapeutic drug monitoring, survival outcomes

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

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