REVIEW ARTICLE
Year : 2016  |  Volume : 7  |  Issue : 2  |  Page : 62-71

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


Department of Pediatric Hematology/Oncology, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, Cleveland, OH, USA

Correspondence Address:
Rachel A Egler
Department of Pediatric Hematology/Oncology, Case Western Reserve University School of Medicine, Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.184769

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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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