Antibodies against polyethylene glycol (PEG) in healthy subjects raise concerns about the efficacy of pegylated drugs. We evaluated the prevalence of antibodies against PEG among patients with acute lymphoblastic leukemia (ALL) prior to and/or immediately after their first dose of pegylated E.coli asparaginase (PEG-ASNase). Serum samples of 701 children, 673 with primary ALL, 28 with relapsed ALL, and 188 adults with primary ALL were analyzed for anti-PEG IgG and IgM. Measurements in 58 healthy infants served as reference to define cut-points for antibody-positive and -negative samples. Anti-PEG antibodies were detected in ALL patients prior the first PEG-ASNase with a prevalence of 13.9% (anti-PEG IgG) and 29.1% (anti-PEG IgM). After administration of PEG-ASNase the prevalence of anti-PEG antibodies decreased to 4.2% for anti-PEG IgG and to 4.5% for anti-PEG IgM. Pre-existing anti-PEG antibodies did not inhibit PEG-ASNase activity but significantly reduced PEGASNase activity levels in a concentration dependent manner. Although pre-existing anti-PEG antibodies did not boost, pre-existing anti-PEG IgG were significantly associated with firstexposure hypersensitivity reactions (CTCAE grade 2) (p.

Center of Laboratory Medicine University Hospital Muenster Albert Schweitzer Campus 1 48149 Muenster

Department of Medicine University Hospital Frankfurt a M

Department of Pediatric Hematology and Oncology Medical School Hannover

Department of Pediatric Hematology and Oncology St Anna Children's Hospital Department of Pediatrics and Adolescent Medicine Medical University of Vienna Vienna

Department of Pediatric Hematology and Oncology University Children's Hospital Muenster

Department of Pediatric Hematology and Oncology University Hospital Motol Praha Czech Republic

Department of Pediatrics University Medical Center Schleswig Holstein Campus Kiel Kiel

Department of Pharmaceutical and Medical Chemistry Clinical Pharmacy University of Muenster

Departments of Biochemistry and Oncology The Children's Hospital at Westmead Sydney Pharmacy School University of Sydney Sydney

Departments of Pediatric Oncology Hematology and of General Pediatrics Charité University Medicine Berlin Berlin

Institute of Biostatistics and Clinical Research University of Muenster

Laboratory of Cancer Pharmacology Department of Oncology Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan

Pediatric Hematology Oncology Unit Department of Pediatrics University of Milano Bicocca MBBM Foundation ASST Monza Monza

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PEGylated Asparaginase in Children with Acute Lymphoblastic Leukemia Treated within the AIEOP-BFM ALL 2009 Trial: Population Pharmacokinetics and Drug Exposure

Impact of Antibodies Against Polyethylene Glycol on the Pharmacokinetics of PEGylated Asparaginase in Children with Acute Lymphoblastic Leukaemia: A Population Pharmacokinetic Approach