BACKGROUND: In the international AIEOP-BFM ALL 2009 trial, asparaginase (ASE) activity was monitored after each dose of pegylated Escherichia coli ASE (PEG-ASE). Two methods were used: the aspartic acid β-hydroxamate (AHA) test and medac asparaginase activity test (MAAT). As the latter method overestimates PEG-ASE activity because it calibrates using E. coli ASE, method comparison was performed using samples from the AIEOP-BFM ALL 2009 trial. METHODS: PEG-ASE activities were determined using MAAT and AHA test in 2 sets of samples (first set: 630 samples and second set: 91 samples). Bland-Altman analysis was performed on ratios between MAAT and AHA tests. The mean difference between both methods, limits of agreement, and 95% confidence intervals were calculated and compared for all samples and samples grouped according to the calibration ranges of the MAAT and the AHA test. RESULTS: PEG-ASE activity determined using the MAAT was significantly higher than when determined using the AHA test (P < 0.001; Wilcoxon signed-rank test). Within the calibration range of the MAAT (30-600 U/L), PEG-ASE activities determined using the MAAT were on average 23% higher than PEG-ASE activities determined using the AHA test. This complies with the mean difference reported in the MAAT manual. With PEG-ASE activities >600 U/L, the discrepancies between MAAT and AHA test increased. Above the calibration range of the MAAT (>600 U/L) and the AHA test (>1000 U/L), a mean difference of 42% was determined. Because more than 70% of samples had PEG-ASE activities >600 U/L and required additional sample dilution, an overall mean difference of 37% was calculated for all samples (37% for the first and 34% for the second set). CONCLUSIONS: Comparison of the MAAT and AHA test for PEG-ASE activity confirmed a mean difference of 23% between MAAT and AHA test for PEG-ASE activities between 30 and 600 U/L. The discrepancy increased in samples with >600 U/L PEG-ASE activity, which will be especially relevant when evaluating high PEG-ASE activities in relation to toxicity, efficacy, and population pharmacokinetics.

Clinica Pediatrica Ospedale S Gerardo Università di Milano Bicocca Monza Italy

Department of Biochemistry and Oncology The Children's Hospital at Westmead

Department of Oncology and Onco Hematology University of Milan Milan Italy

Department of Paediatric Haematology and Oncology Hannover Medical School Hannover

Department of Pediatric Hematology and Oncology St Anna Children's Hospital

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

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

Department of Pediatrics and Adolescent Medicine Medical University Vienna Germany

Faculty of Pharmacy University of Sydney Sydney Australia

Institute of Biostatistics and Clinical Research University of Muenster Muenster Germany

Klinik für Allgemeine Pädiatrie Universitätsklinikum Schleswig Holstein Campus Kiel Kiel Germany

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

Pediatric Hematology Oncology Schneider Children's Medical Center Petah Tikva

Sackler Faculty of Medicine Tel Aviv University Tel Aviv Israel

Citace poskytuje Crossref.org

Incidence and Characteristics of Hypersensitivity Reactions to PEG-asparaginase Observed in 6136 Children With Acute Lymphoblastic Leukemia Enrolled in the AIEOP-BFM ALL 2009 Study Protocol

Asparagine levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia treated with pegylated-asparaginase in the induction phase of the AIEOP-BFM ALL 2009 study