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In this article, we discuss important considerations for such studies, including those related to which patients are appropriate targets of deintensification efforts and which elements of therapy are or are not appropriate candidates for omission.<\/jats:p>","DOI":"10.1182\/hematology.2025000709","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T14:08:05Z","timestamp":1764943685000},"page":"229-235","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":1,"title":["The challenge of deintensifying chemotherapy for children and adolescents with B-ALL in the immunotherapy era"],"prefix":"10.1182","volume":"2025","author":[{"given":"Sumit","family":"Gupta","sequence":"first","affiliation":[{"name":"1 Hospital for Sick Children, University of Toronto, Toronto, Canada"},{"name":"2 Division of Haematology\u2013Oncology; Faculty of Medicine, University of Toronto, Toronto, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"McNeer","sequence":"additional","affiliation":[{"name":"3 Division of Pediatric Hematology\u2013Oncology, University of Utah, Primary Children's Hospital, Salt Lake City, UT"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"O'Brien","sequence":"additional","affiliation":[{"name":"4 Children's Hospital Colorado and the University of Colorado School of Medicine, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Rau","sequence":"additional","affiliation":[{"name":"5 Seattle Children's Hospital, Seattle, WA"},{"name":"6 Ben Towne Center for Childhood Cancer and Blood Disorders Research and Department of Pediatrics, Fred Hutchinson Cancer Center, University of Washington, Seattle, WA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Teachey","sequence":"additional","affiliation":[{"name":"7 Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, PA"},{"name":"8 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"issue":"4","key":"2025120616324903600_hem2025000709C1","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1053\/j.seminhematol.2013.10.001","article-title":"Genomic characterization of childhood acute lymphoblastic leukemia","volume":"50","author":"Mullighan","year":"2013","journal-title":"Semin Hematol"},{"issue":"16","key":"2025120616324903600_hem2025000709C2","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1056\/NEJMra1400972","article-title":"Acute lymphoblastic leukemia in children","volume":"373","author":"Hunger","year":"2015","journal-title":"N Engl J Med"},{"issue":"12","key":"2025120616324903600_hem2025000709C3","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1182\/blood-2008-01-132837","article-title":"Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study","volume":"111","author":"Borowitz","year":"2008","journal-title":"Blood"},{"issue":"21","key":"2025120616324903600_hem2025000709C4","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1182\/blood.V124.21.793.793","article-title":"Outstanding outcome for children with standard risk-low (SR-Low) acute lymphoblastic leukemia (ALL) and no benefit to intensified peg-asparaginase (PEG-ASNase) therapy: results of Children's Oncology Group (COG) Study AALL0331","volume":"124","author":"Mattano","year":"2014","journal-title":"Blood"},{"issue":"1","key":"2025120616324903600_hem2025000709C5","first-page":"140","article-title":"Intensification of oral methotrexate is not superior to standard methotrexate dosing during maintenance in children with National Cancer Institute (NCI) standard-risk B actue lymphoblastic leukemia (SR B-ALL): a report from the Children's Oncology Group (COG) study AALL0932","volume":"130","author":"Angiolillo","year":"2017","journal-title":"Blood"},{"issue":"8","key":"2025120616324903600_hem2025000709C6","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1200\/JCO.23.01388","article-title":"Four additional doses of PEG-L- asparaginase during the consolidation phase in the AIEOP-BFM ALL 2009 protocol do not improve outcome and increase toxicity in high-risk ALL: results of a randomized study","volume":"42","author":"Conter","year":"2024","journal-title":"J Clin Oncol"},{"issue":"suppl 1","key":"2025120616324903600_hem2025000709C7","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1182\/blood-2022-160129","article-title":"High dose methotrexate does not reduce the risk of CNS relapse in children and young adults with acute lymphoblastic leukaemia and lymphoblastic lymphoma. 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