{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T05:15:06Z","timestamp":1789017306780,"version":"build-2803163510"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T00:00:00Z","timestamp":1573689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) in children is challenging and new treatment options are needed. Bortezomib is a proteasome inhibitor with activity in pediatric acute lymphoblastic leukemia. Adding bortezomib to standard reinduction chemotherapy in relapsed and refractory pediatric ALL has produced very good response rates in prior studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated bortezomib in combination with reinduction therapy (ALL R3) in 10 children with relapsed or refractory ALL. Bortezomib (1.3\u00a0mg\/m<jats:sup>2<\/jats:sup>\/dose) was administered to patients on days 1, 4, 8, and 11. In addition, patients received mitoxantrone, dexamethasone, pegaspargase, vincristine, and intrathecal methotrexate over 4\u00a0weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 10 patients, eight (80%) achieved a complete remission (CR) or complete remission with incomplete recovery (CRi). Of the patients in CR, two had undetectable minimal residual disease by flow cytometry\u00a0(&lt;0.01%). Five patients were subsequently treated with a stem cell transplant. All eight patients that achieved CR or CRi eventually relapsed. One patient remains alive following treatment with tisagenlecleucel after relapse. Grade 3 or higher infections occurred in four out of 10 patients, and other toxicities commonly associated with bortezomib were not seen.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In children with relapsed or refractory ALL, the addition of bortezomib to reinduction chemotherapy that includes mitoxantrone produces a complete response in the majority of cases and does not lead to excessive toxicity.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.28062","type":"journal-article","created":{"date-parts":[[2019,11,14]],"date-time":"2019-11-14T11:22:00Z","timestamp":1573730520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Treatment of children with relapsed and refractory acute lymphoblastic leukemia with mitoxantrone, vincristine, pegaspargase, dexamethasone, and bortezomib"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5690-0855","authenticated-orcid":false,"given":"Keith J.","family":"August","sequence":"first","affiliation":[{"name":"Department of Pediatrics Children's Mercy Hospitals and Clinics  Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2482-5608","authenticated-orcid":false,"given":"Erin M.","family":"Guest","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Mercy Hospitals and Clinics  Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Lewing","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Mercy Hospitals and Clinics  Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Allyson","family":"Hays","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Mercy Hospitals and Clinics  Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan S.","family":"Gamis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Children's Mercy Hospitals and Clinics  Kansas City Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1400972"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.99.153"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)62002-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2005.10.001"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0135-z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21214"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22456"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-04-418640"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.6634"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15919"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14505"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2235-z"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15233"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2016.4204"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4541"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-149385"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07573.x"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2950"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2008.07499.x"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28062","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pbc.28062","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.28062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T23:10:41Z","timestamp":1694128241000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.28062"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,14]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1002\/pbc.28062"],"URL":"https:\/\/doi.org\/10.1002\/pbc.28062","archive":["Portico"],"relation":{},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,14]]},"assertion":[{"value":"2019-06-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-10-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e28062"}}