title: Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. jonathan.armstrong@usc.edu
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Armstrong
authors.forename: Georg
authors.initials: G
authors.lastname: Hempel
authors.forename: Susanne
authors.initials: S
authors.lastname: Koling
authors.forename: Linda S
authors.initials: LS
authors.lastname: Chan
authors.forename: Timothy
authors.initials: T
authors.lastname: Fisher
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Meiselman
authors.forename: George
authors.initials: G
authors.lastname: Garratty
mesh_terms: D000372:Agglutination Tests / Q000379:methods; D000906:Antibodies / Q000097:blood*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D001215:Asparaginase / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D011092:Polyethylene Glycols / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000188:drug therapy*; D015203:Reproducibility of Results; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase