{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T12:13:43Z","timestamp":1777637623141,"version":"3.51.4"},"reference-count":30,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T00:00:00Z","timestamp":1513641600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10 CA180886"],"award-info":[{"award-number":["U10 CA180886"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U10 CA180899"],"award-info":[{"award-number":["U10 CA180899"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006058","name":"St. Baldrick's Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006058","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2018,3,15]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Children, adolescents, and young adults with very high\u2010risk (VHR) B acute lymphoblastic leukemia (B\u2010ALL) have poor outcomes, and novel therapies are needed for this subgroup. The AALL1131 study evaluated postinduction therapy using cyclophosphamide (CPM), etoposide (ETOP), and clofarabine (CLOF) for patients with VHR B\u2010ALL.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Patients who were 1 to 30 years old and had VHR B\u2010ALL received modified Berlin\u2010Frankfurt\u2010M\u00fcnster therapy after induction and were randomized to 1) CPM, cytarabine, mercaptopurine, vincristine (VCR), and pegaspargase (control arm), 2) CPM, ETOP, VCR, and pegaspargase (experimental arm 1), or 3) CPM, ETOP, CLOF (30 mg\/m<jats:sup>2<\/jats:sup>\/d \u00d7 5), VCR, and pegaspargase (experimental arm 2) during the second half of consolidation and delayed intensification.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>The rates of grade 4\/5 infections and grade 3\/4 pancreatitis were significantly increased in experimental arm 2. The dose of CLOF was, therefore, reduced to 20 mg\/m<jats:sup>2<\/jats:sup>\/d \u00d7 5, and myeloid growth factor was required after CLOF administration. Despite these changes, 4 of 39 patients (10.3%) developed grade 4 infections, with 1 of these patients developing a grade 5 acute kidney injury attributed to CLOF, whereas only 1 of 46 patients (2.2%) in experimental arm 1 developed grade 4 infections, and there were no grade 4\/5 infections in the control arm (n = 20). Four patients in experimental arm 2 had prolonged cytopenias for &gt;60 days, whereas none did in the control arm or experimental arm 1. Counts failed to recover for 2 of these patients, one having a grade 5 acute kidney injury and the other removed from protocol therapy; both events occurred 92 days after the start of consolidation part 2.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>In AALL1131, CLOF, administered with CPM and ETOP, was associated with unacceptable toxicity. <jats:bold><jats:italic>Cancer<\/jats:italic> 2018;124:1150\u20109<\/jats:bold>. \u00a9 <jats:italic>2017 American Cancer Society<\/jats:italic>.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.31099","type":"journal-article","created":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T13:02:39Z","timestamp":1513688559000},"page":"1150-1159","source":"Crossref","is-referenced-by-count":57,"title":["Toxicity associated with intensive postinduction therapy incorporating clofarabine in the very high\u2010risk stratum of patients with newly diagnosed high\u2010risk B\u2010lymphoblastic leukemia: A report from the Children's Oncology Group study AALL1131"],"prefix":"10.1002","volume":"124","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7820-9635","authenticated-orcid":false,"given":"Wanda L.","family":"Salzer","sequence":"first","affiliation":[{"name":"US Army Medical Research and Materiel Command Fort Detrick Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael J.","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Medical College of Wisconsin Children's Hospital of Wisconsin Milwaukee Wisconsin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meenakshi","family":"Devidas","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Colleges of Medicine and Public Health &amp; Health Professions University of Florida Gainesville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Si","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Colleges of Medicine and Public Health &amp; Health Professions University of Florida Gainesville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lia","family":"Gore","sequence":"additional","affiliation":[{"name":"Center for Cancer and Blood Disorders, Children's Hospital Colorado University of Colorado School of Medicine Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric C.","family":"Larsen","sequence":"additional","affiliation":[{"name":"Maine Children's Cancer Program Scarborough Maine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Borowitz","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins Medical Institutions Baltimore Maryland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brent","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine University of Washington Seattle Washington"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nyla A.","family":"Heerema","sequence":"additional","affiliation":[{"name":"Department of Pathology Ohio State University School of Medicine Columbus Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Genetics University of Alabama at Birmingham Birmingham Alabama"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne M.","family":"Hilden","sequence":"additional","affiliation":[{"name":"Children's Hospital Colorado University of Colorado School of Medicine Aurora Colorado"},{"name":"Department of Pediatrics University of Colorado School of Medicine Aurora Colorado"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mignon L.","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Benioff Children's Hospital University of California at San 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