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In induction, patients received two PEG\u2010EcASNase doses, 14\u00a0days apart. Post\u2010induction, non\u2010high\u2010risk patients (Regimens A, B) received 1\u20132 doses in delayed intensification (DI) while high\u2010risk Regimen C patients received 6\u201310 PEG\u2010EcASNase doses, including two in DI. Trial substudies monitored asparaginase (ASNase) activity, ASNase\u2010related toxicity and ASNase\u2010associated antibodies (total, 1112 patients). Median (interquartile range) trough plasma ASNase activity (14\u00a0\u00b1\u00a02\u00a0days post dose) following first and second induction doses and first DI dose was respectively 217\u00a0iu\/l (144\u2013307\u00a0iu\/l), 265\u00a0iu\/l (165\u2013401\u00a0iu\/l) and 292\u00a0iu\/l (194\u2013386\u00a0iu\/l); 15% (138\/910) samples showed subthreshold ASNase activity (&lt;100\u00a0iu\/l) at any trough time point. Older age was associated with lower (regression coefficient \u22129.5;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001) and DI time point with higher ASNase activity (regression coefficient 29.9;\n                    <jats:italic>p<\/jats:italic>\n                    \u00a0&lt;\u00a00.0001). Clinical hypersensitivity was observed in 3.8% (UKALL 2003) and 6% (UKALL 2011) of patients, and in 90% or more in Regimen C. A 7% (10\/149) silent inactivation rate was observed in UKALL 2003. PEG\u2010EcASNase schedule in UKALL paediatric trials is associated with low toxicity but wide interpatient variability. Therapeutic drug monitoring potentially permits optimisation through individualised asparaginase dosing.\n                  <\/jats:p>","DOI":"10.1111\/bjh.18158","type":"journal-article","created":{"date-parts":[[2022,3,29]],"date-time":"2022-03-29T06:01:16Z","timestamp":1648533676000},"page":"142-150","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Activity and toxicity of intramuscular 1000\n                    <scp>iu<\/scp>\n                    \/m\n                    <sup>2<\/sup>\n                    polyethylene glycol\u2010\n                    <i>E. coli<\/i>\n                    <scp>L\u2010asparaginase<\/scp>\n                    in the\n                    <scp>UKALL<\/scp>\n                    2003 and\n                    <scp>UKALL<\/scp>\n                    2011 clinical trials"],"prefix":"10.1111","volume":"198","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5926-5167","authenticated-orcid":false,"given":"Jasmeet","family":"Sidhu","sequence":"first","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashish Narayan","family":"Masurekar","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manash Pratim","family":"Gogoi","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Fong","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasos","family":"Ioannou","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taha","family":"Lodhi","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona","family":"Parker","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jizhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy A.","family":"Kirkwood","sequence":"additional","affiliation":[{"name":"Cancer Research UK &amp; UCL Cancer Trials Centre UCL Cancer Institute, University College  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony V.","family":"Moorman","sequence":"additional","affiliation":[{"name":"Wolfson Childhood Cancer Research Centre Northern Institute for Cancer Research, Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiranmoy","family":"Das","sequence":"additional","affiliation":[{"name":"Interdisciplinary Statistical Research Unit Indian Statistical Institute  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Goulden","sequence":"additional","affiliation":[{"name":"Department of Haematology Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay","family":"Vora","sequence":"additional","affiliation":[{"name":"Department of Haematology Great Ormond Street Hospital for Children  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-9649","authenticated-orcid":false,"given":"Vaskar","family":"Saha","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6769-3847","authenticated-orcid":false,"given":"Shekhar","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Tata Translational Cancer Research Centre Tata Medical Center  Kolkata India"},{"name":"Department of Paediatric Haematology and Oncology Tata Medical Center  Kolkata India"},{"name":"Childrens Cancer Group, Division of Cancer Sciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2021.08.025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.1003056"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.6.1986"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/esmoopen-2020-000977"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(15)00363-0"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-10-534347"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.18.01877"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2018.1542146"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2018.206433"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26686"},{"issue":"1","key":"e_1_2_8_12_1","first-page":"24","article-title":"A pharmacological study on pegylated asparaginase used in front\u2010line treatment of children with acute lymphoblastic leukemia","volume":"91","author":"Rizzari C","year":"2006","journal-title":"Haematologica"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.165"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.12865"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02292"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.26651"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.13847"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70243-8"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(12)70600-9"},{"issue":"1","key":"e_1_2_8_20_1","article-title":"UKALL 2011: Randomised trial investigating a short induction dexamethasone schedule for children and young adults with acute lymphoblastic Leukaemia","volume":"130","author":"Goulden NJ","year":"2017","journal-title":"Blood"},{"key":"e_1_2_8_21_1","unstructured":"GouldenN.UKALL 2011 [cited 2022 Mar 23]. 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