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Hypersensitivity with inactivation of asparaginase is common and often associated with severe allergic reactions. This study aims to comprehensively analyse asparaginase enzyme activity (AEA) pharmacokinetics, validate a previously developed pharmacokinetic model based on intravenous administration and evaluate its capability to detect changes in clearance before inactivation in patients treated with intramuscular peg\u2010asparaginase. The study, covering 644 patients aged 1\u201345 with ALL under the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 Protocol (February 2017\u2013December 2022, in Nordic and Baltic countries), included 3003 AEA samples. Sampling occurred 14\u2009days post peg\u2010asparaginase doses, with additional sampling between doses. The incidence of inactivation was 15.2%. Utilizing the pharmacokinetic model, estimates revealed an 87.8% sensitivity and 65.5% specificity for detecting increased peg\u2010asparaginase clearance over time in patients experiencing inactivation. Identification of increased clearance preceding inactivation in the NOPHO ALL2008 dataset highlights the potential of pharmacokinetic sampling to predict inactivation and enable timely intervention before clinical manifestation, with further refinement and inclusion of additional protocols into a unified model offering the promise of improving clinicians' ability to assess individual patient risk.<\/jats:p>","DOI":"10.1111\/bjh.70145","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:40:34Z","timestamp":1757310034000},"page":"1920-1929","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early prediction of subsequent peg\u2010asparaginase inactivation in acute lymphoblastic leukaemia patients\u2014A\n                    <scp>NOPHO ALL2008<\/scp>\n                    study"],"prefix":"10.1111","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8857-8629","authenticated-orcid":false,"given":"Merete","family":"Dam","sequence":"first","affiliation":[{"name":"Department of Paediatrics and Adolescent Medicine Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Aarhus University  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddalena","family":"Centanni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Centanni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena E.","family":"Friberg","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Uppsala University  Uppsala 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