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L-asparaginase in the treatment of patients with acute lymphoblastic leukemia
Open accessAbstract
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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“L-asparaginase has been found to be effective in the treatment of ALL and is included in standard chemotherapy regimens for this disease (Table 1)(Egler et al., 2016).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Egler et al., 2016
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Metadata
- 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
- 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
- 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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