{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:19:39Z","timestamp":1791037179975,"version":"4.1.0"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2010,4,20]],"date-time":"2010-04-20T00:00:00Z","timestamp":1271721600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4\u2010drug induction chemotherapy with vincristine, dexamethasone, pegylated\n                      <jats:sc>L<\/jats:sc>\n                      \u2010asparaginase, and doxorubicin (VXLD) in children with relapsed ALL.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose\u2010limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ). One patient had dose\u2010limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The combination of bortezomib (1.3\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3\u2009mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      cohort for a phase II estimate of response. Study registered at\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\/ct2\/show\/NCT00440726\">http:\/\/clinicaltrials.gov\/ct2\/show\/NCT00440726<\/jats:ext-link>\n                      ). Pediatr Blood Cancer 2010;55:254\u2013259. \u00a9 2010 Wiley\u2010Liss, Inc.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.22456","type":"journal-article","created":{"date-parts":[[2010,4,20]],"date-time":"2010-04-20T19:02:21Z","timestamp":1271790141000},"page":"254-259","source":"Crossref","is-referenced-by-count":101,"title":["Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium"],"prefix":"10.1002","volume":"55","author":[{"given":"Yoav","family":"Messinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Gaynon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Raetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond","family":"Hutchinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"DuBois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Glade\u2010Bender","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Sposto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette","family":"van der Giessen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Eckroth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce C.","family":"Bostrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,6,25]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2008.251"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.5856"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.1414"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2950"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0093-7754(01)90034-X"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.11.030"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2006.11.001"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.3816\/CLM.2002.n.011"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2006.06170.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.8-6-508"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.21214"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-03-0508"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-06-2173"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0135-z"},{"key":"e_1_2_5_16_2","first-page":"203","article-title":"Morphoproteomics and bortezomib\/dexamethasone\u2010induced response in relapsed acute lymphoblastic leukemia","volume":"34","author":"Brown RE","year":"2004","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4626"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(19980730)17:14<1537::AID-SIM872>3.0.CO;2-F"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4541"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402953"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-0081-1"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-01-199604"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.6.4.4226"}],"container-title":["Pediatric Blood &amp; 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