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Previous studies suggest proteasome inhibition with chemotherapy improves relapse <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> response rates. This phase 2 Children's Oncology Group study tested the hypothesis that adding the proteasome inhibitor bortezomib to chemotherapy increases complete response rates (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>2). Evaluable patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a0135, 103 B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>, 22 T\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>, 10 T\u2010lymphoblastic lymphoma) were treated with reinduction chemotherapy plus bortezomib. Overall <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>2 rates were 68\u00a0\u00b1\u00a05% for precursor B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> patients (&lt;21\u00a0years of age), 63\u00a0\u00b1\u00a07% for very early relapse (&lt;18\u00a0months from diagnosis) and 72\u00a0\u00b1\u00a06% for early relapse (18\u201336\u00a0months from diagnosis). Relapsed T\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> patients had an encouraging <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>2 rate of 68\u00a0\u00b1\u00a010%. End of induction minimal residual disease (<jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>) significantly predicted survival. <jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content> negative (<jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>neg; <jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content> &lt;0\u00b701%) rates increased from 29% (post\u2010cycle 1) to 64% following cycle 3. Very early relapse, end\u2010of\u2010induction <jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>neg precursor B\u2010<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> patients had 70\u00a0\u00b1\u00a014% 3\u2010year event\u2010free (<jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>) and overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) rates, vs. 3\u2010year <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> of 0\u20133% (<jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70001) for <jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>pos (<jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content> \u22650\u00b701) patients. Early relapse patients had similar outcomes (<jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>neg 3\u2010year <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> 58\u201365% vs. <jats:styled-content style=\"fixed-case\">MRD<\/jats:styled-content>pos 10\u201319%, <jats:styled-content style=\"fixed-case\">EFS <\/jats:styled-content><jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b70014). These data suggest that adding bortezomib to chemotherapy in certain <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> subgroups, such as T\u2010cell <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>, is worthy of further investigation. This study is registered at <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinical.trials.gov\">http:\/\/www.clinical.trials.gov<\/jats:ext-link> as <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>00873093.<\/jats:p>","DOI":"10.1111\/bjh.15919","type":"journal-article","created":{"date-parts":[[2019,4,8]],"date-time":"2019-04-08T01:58:53Z","timestamp":1554688733000},"page":"274-285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":109,"title":["Bortezomib reinduction chemotherapy in high\u2010risk <scp>ALL<\/scp> in first relapse: a report from the Children's Oncology Group"],"prefix":"10.1111","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8293-4242","authenticated-orcid":false,"given":"Terzah M.","family":"Horton","sequence":"first","affiliation":[{"name":"Texas Children's Cancer and Hematology Centers at Baylor College of Medicine Houston TX 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