{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:44:38Z","timestamp":1790138678018,"version":"4.0.1"},"reference-count":24,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cyclin D has been shown to play an essential role in acute lymphoblastic leukemia (ALL) initiation and progression, providing rationale for targeting the CDK4\/6\u2010cyclin D complex that regulates cell cycle progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Procedure<\/jats:title>\n                    <jats:p>\n                      The Children's Oncology Group AINV18P1 phase 1 trial evaluated the CDK4\/6 inhibitor, palbociclib, in combination with standard four\u2010drug re\u2010induction chemotherapy in children and young adults with relapsed\/refractory B\u2010 and T\u2010cell lymphoblastic leukemia (ALL) and lymphoma. Palbociclib (50\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose) was administered orally once daily for 21 consecutive days, first as a single agent (Days 1\u20133) and subsequently combined with re\u2010induction chemotherapy. This two\u2010part study was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D), followed by an expansion pharmacokinetic cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twelve heavily pretreated patients enrolled, all of whom were evaluable for toxicity. One dose\u2010limiting hematologic toxicity (DLT) occurred at the starting dose of 50\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/dose orally for 21\u00a0days. No additional DLTs were observed in the dose determination or pharmacokinetic expansion cohorts, and overall rates of grade 3\/4 nonhematologic toxicities were comparable to those observed with the chemotherapy platform alone. Five complete responses were observed, two among four patients with T\u2010ALL and three among seven patients with B\u2010ALL. Pharmacokinetic studies showed similar profiles with both liquid and capsule formulations of palbociclib.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Palbociclib in combination with re\u2010induction chemotherapy was well tolerated with a RP2D of 50\u00a0mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \/day for 21\u00a0days. Complete responses were observed among heavily pretreated patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pbc.30609","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T22:58:35Z","timestamp":1691535515000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Palbociclib in combination with chemotherapy in pediatric and young adult patients with relapsed\/refractory acute lymphoblastic leukemia and lymphoma: A Children's Oncology Group study (AINV18P1)"],"prefix":"10.1002","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8547-1658","authenticated-orcid":false,"given":"Elizabeth A.","family":"Raetz","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Perlmutter Cancer Center NYU Langone Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T.","family":"Teachey","sequence":"additional","affiliation":[{"name":"Division of Oncology and Center for Childhood Cancer Research Children's Hospital of Philadelphia Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Minard","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Translational Research Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Liu","sequence":"additional","affiliation":[{"name":"Children's Oncology Group Monrovia California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8589-1804","authenticated-orcid":false,"given":"Robin E.","family":"Norris","sequence":"additional","affiliation":[{"name":"Cancer and Blood Diseases Institute Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA"},{"name":"Department of Pediatrics University of Cincinnati School of Medicine Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina Z.","family":"Denic","sequence":"additional","affiliation":[{"name":"Division of Oncology Research, Department of Oncology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Reid","sequence":"additional","affiliation":[{"name":"Division of Oncology Research, Department of Oncology Mayo Clinic Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8090-0986","authenticated-orcid":false,"given":"Nikki A.","family":"Evensen","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Perlmutter Cancer Center NYU Langone Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2546-4616","authenticated-orcid":false,"given":"Lia","family":"Gore","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Colorado School of Medicine Aurora Colorado USA"},{"name":"Children's Hospital Colorado Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Oncology St Jude Children's Research Hospital Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4099-4700","authenticated-orcid":false,"given":"Mignon L.","family":"Loh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and the Ben Towne Center for Childhood Cancer Research University of Washington Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brenda J.","family":"Weigel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Masonic Cancer Center University of Minnesota Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Perlmutter Cancer Center NYU Langone Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.10008"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.22.2950"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0094-0"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2016.03.002"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2016.26"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-16-2825"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1551"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00016"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.03.012"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0379-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28879"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00301-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.09.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279410"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.16.1414"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.7712"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22414"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.59.0745"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.8800"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/08880018.2016.1251518"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-11-0509"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2011.177"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.792"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60352-8"}],"container-title":["Pediatric Blood &amp; Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pbc.30609","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T09:04:29Z","timestamp":1695632669000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pbc.30609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,8]]},"references-count":24,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/pbc.30609"],"URL":"https:\/\/doi.org\/10.1002\/pbc.30609","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.22541\/au.167989700.00930360\/v1","asserted-by":"object"}]},"ISSN":["1545-5009","1545-5017"],"issn-type":[{"value":"1545-5009","type":"print"},{"value":"1545-5017","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,8]]},"assertion":[{"value":"2023-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e30609"}}