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The prognostic impact of <jats:italic>IKZF1<\/jats:italic> status, in conjunction with minimal\/measurable residual disease (MRD), was evaluated within the MRD\u2010guided TPOG\u2010ALL\u20102013 protocol using 412 newly diagnosed B\u2010ALL patients aged 1\u201318. <jats:italic>IKZF1<\/jats:italic> status was determined using multiplex ligation\u2010dependent probe amplification. <jats:italic>IKZF1<\/jats:italic> deletions, when co\u2010occurring with <jats:italic>CDKN2A<\/jats:italic>, <jats:italic>CDKN2B<\/jats:italic>, <jats:italic>PAX5<\/jats:italic> or PAR1 region deletions in the absence of <jats:italic>ERG<\/jats:italic> deletions, were termed <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup>. Both <jats:italic>IKZF1<\/jats:italic> deletion (14.6%) and <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup> (7.8%) independently predicted poorer outcomes in B\u2010ALL. <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup> was observed in 4.1% of Philadelphia\u2010negative ALL, with a significantly lower 5\u2010year event\u2010free survival (53.9%) compared to <jats:italic>IKZF1<\/jats:italic> deletion alone (83.8%) and wild\u2010type <jats:italic>IKZF1<\/jats:italic> (91.3%) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Among patients with Day 15 MRD \u22650.01%, provisional high\u2010risk patients with <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup> exhibited the worst outcomes in event\u2010free survival (42.0%), relapse\u2010free survival (48.0%) and overall survival (72.7%) compared to other groups (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). Integration of <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup> and positive Day 15 MRD identified a subgroup of Philadelphia\u2010negative B\u2010ALL with a 50% risk of relapse. This study highlights the importance of assessing <jats:italic>IKZF1<\/jats:italic><jats:sup><jats:italic>plus<\/jats:italic><\/jats:sup> alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.<\/jats:p>","DOI":"10.1111\/bjh.19338","type":"journal-article","created":{"date-parts":[[2024,3,14]],"date-time":"2024-03-14T00:04:36Z","timestamp":1710374676000},"page":"1344-1353","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Refining risk stratification in paediatric <scp>B\u2010acute<\/scp> lymphoblastic leukaemia: Combining <scp><i>IKZF1<\/i><sup>plus<\/sup><\/scp> and Day 15 <scp>MRD<\/scp> positivity"],"prefix":"10.1111","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9721-167X","authenticated-orcid":false,"given":"Hsi\u2010Che","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hematology\u2010Oncology MacKay Children's Hospital and MacKay Medical College  Taipei Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying\u2010Jung","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine Chang Gung Memorial Hospital at Linkou  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tang\u2010Her","family":"Jaing","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Chang Gung Children's Hospital at Linkou  Taoyuan Taiwan"},{"name":"College of Medicine Chang Gung University  Taoyuan Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang\u2010Hsi","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Chung Shan Medical University Hospital  Taichung 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