{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:21:56Z","timestamp":1790842916575,"version":"4.1.0"},"reference-count":33,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"20","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2016,7,10]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Survival for children and young adults with high-risk B-acute lymphoblastic leukemia has improved significantly, but 20% to 25% of patients are not cured. Children\u2019s Oncology Group study AALL0232 tested two interventions to improve survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients and Methods<\/jats:title>\n                    <jats:p>Between January 2004 and January 2011, AALL0232 enrolled 3,154 participants 1 to 30 years old with newly diagnosed high-risk B-acute lymphoblastic leukemia. By using a 2 \u00d7 2 factorial design, 2,914 participants were randomly assigned to receive dexamethasone (14 days) versus prednisone (28 days) during induction and high-dose methotrexate versus Capizzi escalating-dose methotrexate plus pegaspargase during interim maintenance 1.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Planned interim monitoring showed the superiority of the high-dose methotrexate regimens, which exceeded the predefined boundary and led to cessation of enrollment in January 2011. At that time, participants randomly assigned to high-dose methotrexate during interim maintenance 1 versus those randomly assigned to Capizzi methotrexate had a 5-year event-free survival (EFS) of 82% versus 75.4% (P = .006). Mature final data showed 5-year EFS rates of 79.6% for high-dose methotrexate and 75.2% for Capizzi methotrexate (P = .008). High-dose methotrexate decreased both marrow and CNS recurrences. Patients 1 to 9 years old who received dexamethasone and high-dose methotrexate had a superior outcome compared with those who received the other three regimens (5-year EFS, 91.2% v 83.2%, 80.8%, and 82.1%; P = .015). Older participants derived no benefit from dexamethasone during induction and experienced excess rates of osteonecrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>High-dose methotrexate is superior to Capizzi methotrexate for the treatment of high-risk B-acute lymphoblastic leukemia, with no increase in acute toxicity. Dexamethasone given during induction benefited younger children but provided no benefit and was associated with a higher risk of osteonecrosis among participants 10 years and older.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.2015.62.4544","type":"journal-article","created":{"date-parts":[[2016,4,26]],"date-time":"2016-04-26T00:24:08Z","timestamp":1461630248000},"page":"2380-2388","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":347,"title":["Dexamethasone and High-Dose Methotrexate Improve Outcome for Children and Young Adults With High-Risk B-Acute Lymphoblastic Leukemia: A Report From Children\u2019s Oncology Group Study AALL0232"],"prefix":"10.1200","volume":"34","author":[{"given":"Eric C.","family":"Larsen","sequence":"first","affiliation":[{"name":"Eric C. Larsen, Maine Children\u2019s Cancer Program, Scarborough, ME; Meenakshi Devidas and Si Chen, University of Florida, Gainesville, FL; Wanda L. Salzer, US Army Medical Research and Materiel Command, Frederick; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT, Mignon L. Loh, University of California, San Francisco, San Francisco, CA; Leonard A. Mattano Jr, HARP Pharma Consulting, Mystic, CT; Catherine Cole, Princess..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Devidas","sequence":"additional","affiliation":[{"name":"Eric C. Larsen, Maine Children\u2019s Cancer Program, Scarborough, ME; Meenakshi Devidas and Si Chen, University of Florida, Gainesville, FL; Wanda L. Salzer, US Army Medical Research and Materiel Command, Frederick; Michael J. Borowitz, Johns Hopkins Medical Institutions, Baltimore, MD; Elizabeth A. Raetz, University of Utah, Salt Lake City, UT, Mignon L. Loh, University of California, San Francisco, San Francisco, CA; Leonard A. 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