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Successful challenges using native E. coli asparaginase after hypersensitivity reactions to PEGylated E. coli asparaginase

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Abstract

Purpose

Asparaginase is an essential component of pediatric acute lymphoblastic leukemia (ALL) therapy. However, asparaginase-induced hypersensitivity reactions can compromise its efficacy either by directly influencing the pharmacokinetics of asparaginase or by leading to a discontinuation of asparaginase treatment. Here, we report successful challenges using native Escherichia coli asparaginase after previous hypersensitivity reactions to both PEGylated E. coli asparaginase and Erwinia asparaginase.

Patients and methods

The two patients included in this case report were diagnosed with B-precursor ALL at St. Jude Children’s Research Hospital and were treated with a common regimen. Both patients developed hypersensitivity reactions to PEGylated E. coli asparaginase and Erwinia asparaginase early in treatment, and they were challenged with native E. coli asparaginase. Serum samples were collected for estimating the pharmacokinetic parameters of each patient during native E. coli asparaginase therapy.

Results

Challenges with native E. coli asparaginase were successful, and asparaginase serum concentrations above therapeutic levels were attained in both patients.

Conclusions

These two cases suggest that some patients can be given native E. coli asparaginase after hypersensitivity reactions to PEGylated asparaginase and achieve therapeutic concentrations of the drug in serum.

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Acknowledgments

The study was supported by the Grants CA 21765, CA 142665, and CA 36401 from the National Cancer Institute, by the American Lebanese Syrian Associated Charities, and by funding from Sigma–Tau Pharmaceuticals for research on the pharmacology of asparaginase.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN, 38105, USA

    C. A. Fernandez, J. C. Panetta, M. R. Wilkinson, A. R. Morrison & M. V. Relling

  2. Department of Oncology, St. Jude Children’s Research Hospital, 262 Danny Thomas Place, MS 260, Memphis, TN, 38105, USA

    E. Stewart, J. T. Sandlund, C. H. Pui, S. Jeha & P. K. Campbell

  3. Department of Medicine, Cincinnati Veterans Affairs Medical Center, Cincinnati, OH, USA

    F. D. Finkelman

  4. Division of Immunology, Allergy and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    F. D. Finkelman

  5. Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, 45267, USA

    F. D. Finkelman

Authors
  1. C. A. Fernandez
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  2. E. Stewart
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  3. J. C. Panetta
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  4. M. R. Wilkinson
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  5. A. R. Morrison
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  6. F. D. Finkelman
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  7. J. T. Sandlund
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  8. C. H. Pui
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  9. S. Jeha
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  10. M. V. Relling
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  11. P. K. Campbell
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Corresponding author

Correspondence to P. K. Campbell.

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Fernandez, C.A., Stewart, E., Panetta, J.C. et al. Successful challenges using native E. coli asparaginase after hypersensitivity reactions to PEGylated E. coli asparaginase. Cancer Chemother Pharmacol 73, 1307–1313 (2014). https://doi.org/10.1007/s00280-014-2464-2

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  • DOI: https://doi.org/10.1007/s00280-014-2464-2

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