Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: A report from the Children's Oncology Group

Pediatr Blood Cancer. 2018 Mar;65(3):10.1002/pbc.26873. doi: 10.1002/pbc.26873. Epub 2017 Nov 1.


Background: Erwinia asparaginase is a Food and Drug Administration approved agent for the treatment of acute lymphoblastic leukemia (ALL) for patients who develop hypersensitivity to Escherichia coli derived asparaginases. Erwinia asparaginase is efficacious, but has a short half-life, requiring six doses to replace one dose of the most commonly used first-line asparaginase, pegaspargase, a polyethylene glycol (PEG) conjugated E. coli asparaginase. Pegcristantaspase, a recombinant PEGylated Erwinia asparaginase with improved pharmacokinetics, was developed for patients with hypersensitivity to pegaspargase. Here, we report a series of patients treated on a pediatric phase 2 trial of pegcrisantaspase.

Procedure: Pediatric patients with ALL or lymphoblastic lymphoma and hypersensitivity to pegaspargase enrolled on Children's Oncology Group trial AALL1421 (Jazz 13-011) and received intravenous pegcrisantaspase. Serum asparaginase activity (SAA) was monitored before and after dosing; immunogenicity assays were performed for antiasparaginase and anti-PEG antibodies and complement activation was evaluated.

Results: Three of the four treated patients experienced hypersensitivity to pegcrisantaspase manifested as clinical hypersensitivity reactions or rapid clearance of SAA. Immunogenicity assays demonstrated the presence of anti-PEG immunoglobulin G antibodies in all three hypersensitive patients, indicating a PEG-mediated immune response.

Conclusions: This small series of patients, nonetheless, provides data, suggesting preexisting immunogenicity against the PEG moiety of pegaspargase and poses the question as to whether PEGylation may be an effective strategy to optimize Erwinia asparaginase administration. Further study of larger cohorts is needed to determine the incidence of preexisting antibodies against PEG-mediated hypersensitivity to pegaspargase.

Keywords: acute lymphoblastic leukemia; asparaginase; hypersensitivity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Asparaginase* / administration & dosage
  • Asparaginase* / adverse effects
  • Asparaginase* / pharmacokinetics
  • Bacterial Proteins* / administration & dosage
  • Bacterial Proteins* / adverse effects
  • Bacterial Proteins* / pharmacokinetics
  • Child
  • Child, Preschool
  • Drug Hypersensitivity / epidemiology*
  • Erwinia / enzymology*
  • Female
  • Humans
  • Infant
  • Male
  • Polyethylene Glycols* / administration & dosage
  • Polyethylene Glycols* / adverse effects
  • Polyethylene Glycols* / pharmacokinetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / epidemiology*


  • Bacterial Proteins
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase