PEGylated E. coli asparaginase desensitization: an effective and feasible option for pediatric patients with acute lymphoblastic leukemia who have developed hypersensitivity to pegaspargase in the absence of asparaginase Erwinia chrysanthemi availability

Pediatr Hematol Oncol. 2019 Aug;36(5):277-286. doi: 10.1080/08880018.2019.1634778. Epub 2019 Jul 12.

Abstract

Asparaginase is an important component of multi-agent chemotherapy for the treatment of pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LLy). Hypersensitivity to the PEGylated form, pegaspargase, is the most common toxicity observed and is ideally addressed by substituting multiple doses of erwinia asparaginase for each subsequent dose of pegaspargase. An international shortage of erwinia asparaginase has limited the therapeutic options for those experiencing pegaspargase hypersensitivity. Here, we report pegaspargase can be safely administered, while maintaining sustained levels of asparaginase activity, to patients who have had a prior hypersensitivity reaction to pegaspargase by using a standard rapid desensitization protocol. Ten patients with prior hypersensitivity reactions to pegaspargase were treated by using a standardized rapid desensitization protocol. Eight patients had therapeutic asparaginase levels between days 4 and 7 of ≥0.05 IU/mL, and seven patients continued to have sustained levels above ≥0.1 IU/mL between days 10 and 14. Based on chemotherapy regimens, five of these patients successfully received more than one dose of pegaspargase utilizing this protocol.

Keywords: Acute lymphoblastic leukemia; desensitization; hypersensitivity; pegaspargase.

Publication types

  • Clinical Trial

MeSH terms

  • Adolescent
  • Adult
  • Asparaginase* / administration & dosage
  • Asparaginase* / adverse effects
  • Asparaginase* / immunology
  • Bacterial Proteins* / administration & dosage
  • Bacterial Proteins* / adverse effects
  • Bacterial Proteins* / immunology
  • Child
  • Child, Preschool
  • Desensitization, Immunologic*
  • Dickeya chrysanthemi / enzymology
  • Drug Hypersensitivity / immunology
  • Drug Hypersensitivity / prevention & control*
  • Escherichia coli / enzymology
  • Female
  • Humans
  • Male
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / adverse effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology

Substances

  • Bacterial Proteins
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase