{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:55:26Z","timestamp":1785333326585,"version":"3.55.0"},"reference-count":40,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,1]],"date-time":"2021-10-01T00:00:00Z","timestamp":1633046400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007316","name":"Division of Cancer Prevention, National Cancer Institute","doi-asserted-by":"publisher","award":["COG NCTN Network Group Operations Centres (5U10CA180886\u201007)"],"award-info":[{"award-number":["COG NCTN Network Group Operations Centres (5U10CA180886\u201007)"]}],"id":[{"id":"10.13039\/100007316","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>High\u2010risk pediatric acute myeloid leukemia confers a poor prognosis, and alternative strategies are needed to improve outcomes. We hypothesized that intensifying induction on the AAML1031 clinical trial would improve outcomes compared to the predecessor trial AAML0531.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients on AAML0531 received cytarabine (1600\u00a0mg\/m<jats:sup>2<\/jats:sup>)\/daunorubicin (150\u00a0mg\/m<jats:sup>2<\/jats:sup>)\/etoposide (ADE) for induction II and patients on AAML1031 received mitoxantrone (48\u00a0mg\/m<jats:sup>2<\/jats:sup>)\/cytarabine (8000\u00a0mg\/m<jats:sup>2<\/jats:sup>) (MA). Stem cell transplant (SCT) conditioning included busulfan\/cyclophosphamide on AAML0531, whereas AAML1031 used busulfan\/fludarabine and liberalized donor eligibility. Patients were included in this analysis if they met high\u2010risk criteria common to the two trials by cytogenics or poor disease response after induction I ADE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MA provided no benefit over ADE at: induction II response (complete response [CR]: 64% vs. 62%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.87; measurable residual disease [MRD]+: 57% vs. 46%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.34); or intensification I response (CR: 79% vs. 94%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.27; MRD+: 27% vs. 20%, <jats:italic>p<\/jats:italic>\u00a0=\u00a01.0). When considered with altered SCT approach, MA did not improve 5\u2010year disease\u2010free survival (24% \u00b1 9% vs. 18% \u00b1 15%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.63) or 5\u2010year overall survival (35% \u00b1 10% vs. 38% \u00b1 18%, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.66). MA was associated with slower neutrophil recovery (median 34 vs. 27\u00a0days, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.007) and platelet recovery (median 29 vs. 24.5\u00a0days, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.04) and longer hospital stay (32 vs. 28\u00a0days, <jats:italic>p<\/jats:italic>\u00a0=\u00a0.01) during induction II.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Intensification of induction II did not improve treatment response or survival, but did increase toxicity and resource utilization. Alternative strategies are urgently needed to improve outcomes for pediatric patients with high\u2010risk acute myeloid leukemia (trials registered at clinicaltrials.gov NCT01371981, NCT00372593).<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29281","type":"journal-article","created":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T01:16:33Z","timestamp":1633137393000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Outcomes of intensification of induction chemotherapy for children with high\u2010risk acute myeloid leukemia: A report from the Children's Oncology Group"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2474-3031","authenticated-orcid":false,"given":"Caitlin W.","family":"Elgarten","sequence":"first","affiliation":[{"name":"Division of Oncology Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Center for Pediatric Clinical Effectiveness Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Wood","sequence":"additional","affiliation":[{"name":"University of Auckland  Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yimei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology, and Informatics, Department of Pediatrics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd A.","family":"Alonzo","sequence":"additional","affiliation":[{"name":"University of Southern California  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Eidenschink","family":"Brodersen","sequence":"additional","affiliation":[{"name":"Hematologics, Inc.  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