Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients

Cancer. 2007 Jul 1;110(1):103-11. doi: 10.1002/cncr.22739.


Background: Rapid clearance of poly(ethylene glycol)-asparaginase (PEG-ASNase) has been reported for up to one-third of patients treated for acute lymphoblastic leukemia (ALL), potentially rendering their treatment ineffective. A 25% occurrence of an antibody against PEG (anti-PEG) was previously reported in healthy blood donors. The objective of the study was to determine whether anti-PEG was associated with rapid clearance PEG-ASNase.

Methods: The investigation reanalyzed stored sera from pediatric patients enrolled in the ALL Berlin-Frankfurt-Muenster 2000 studies. Twenty-eight samples were selected to include 15 subjects with undetectable ASNase activity after receiving PEG-ASNase. Sixteen subjects treated with unmodified ASNase were also included, 8 with low ASNase activity. Sera were tested for anti-PEG using 2 techniques: 1) serology, by agglutination of PEG-coated red blood cells; 2) flow cytometry, by analysis of 10 microm PEG beads stained for bound immunoglobulins. RESULTS. Of the 15 sera from PEG-ASNase-treated patients with undetectable ASNase activity, anti-PEG was detected in 9 by serology and in 12 by flow cytometry. Anti-PEG was detected in 1 PEG-ASNase-treated patient with lower ASNase activity (123 U/L). No relation was observed between anti-PEG and serum ASNase activity for patients treated with unmodified ASNase.

Conclusions: The presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Agglutination Tests / methods
  • Antibodies / blood*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Asparaginase / immunology
  • Asparaginase / pharmacokinetics*
  • Asparaginase / therapeutic use*
  • Child
  • Female
  • Flow Cytometry / methods
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Polyethylene Glycols / pharmacokinetics*
  • Polyethylene Glycols / therapeutic use*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Reproducibility of Results
  • Treatment Outcome


  • Antibodies
  • Antineoplastic Agents
  • Polyethylene Glycols
  • pegaspargase
  • Asparaginase