{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:58:32Z","timestamp":1787241512402,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,5]],"date-time":"2017-06-05T00:00:00Z","timestamp":1496620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We retrospectively analyzed 65 patients with refractory\/relapsed (r\/r) ALL who were treated with blinatumomab for predictors of leukemia response as well as clinical patterns of relapse and resistance with particular focus on downregulation of CD19 expression and extramedullary disease (EM\u2010ALL). The complete remission (CR) rate was 51%, and 15 (45%) responders underwent allogeneic hematopoietic cell transplantation (HCT) in CR. High leukemia burden (bone marrow blasts &gt;50%) (<jats:italic>P<\/jats:italic>\u2009=\u2009.02), history of prior EM\u2010ALL (<jats:italic>P<\/jats:italic>\u2009=\u2009.005), and active EM\u2010ALL at the time of initiating blinatumomab (<jats:italic>P<\/jats:italic>\u2009=\u2009.05) predicted lower CR rate. Among refractory cases, 13 (41%) had evidence of EM\u2010ALL progression, and CD19 expression was negative or dim in 18% and 23%, respectively. Among responders, 20 (61%) subsequently relapsed among whom EM\u2010ALL relapse occurred in 8 (40%) patients, and CD19 expression was negative or dim in 35 and 6% of evaluable cases, respectively. Pretreatment moderate\/strong CD19 expression (<jats:italic>P<\/jats:italic>\u2009=\u2009.01) and history of prior EM\u2010ALL during ALL course (<jats:italic>P<\/jats:italic>\u2009=\u2009.04) were risk factors for developing EM\u2010ALL at progression\/relapse. However, no pretreatment factors predicted progression\/relapse with CD19\u2010negative ALL. Overall\u2010survival (OS) and even\u2010free survival were improved for patients underwent allogeneic HCT compared to responders who did not. Furthermore, OS was superior for patients responded to blinatumomab compared to those who did not. Extramedullary and CD19\u2010negative disease are common during blinatumomab failure in r\/r ALL. In addition to high leukemia burden, concurrent or prior history EM\u2010ALL were associated with lower response to blinatumomab. Higher CD19 expression as well as prior history of EM\u2010ALL were associated with EM\u2010ALL at the time of blinatumomab failure.<\/jats:p>","DOI":"10.1002\/ajh.24783","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T23:46:44Z","timestamp":1494546404000},"page":"858-865","source":"Crossref","is-referenced-by-count":153,"title":["Correlates of resistance and relapse during blinatumomab therapy for relapsed\/refractory acute lymphoblastic leukemia"],"prefix":"10.1002","volume":"92","author":[{"given":"Ibrahim","family":"Aldoss","sequence":"first","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joo","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Information Sciences, Division of Biostatistics City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Stiller","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joycelynne","family":"Palmer","sequence":"additional","affiliation":[{"name":"Department of Pathology City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"O'Donnell","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony S.","family":"Stein","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guido","family":"Marcucci","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Forman","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9129-3424","authenticated-orcid":false,"given":"Vinod","family":"Pullarkat","sequence":"additional","affiliation":[{"name":"Department of Hematology and Hematopoietic Cell Transplantation Gehr Family Center for Leukemia Research, City of Hope Medical Center Duarte California"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,6,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)71170-2"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.56.3247"},{"issue":"1","key":"e_1_2_5_4_1","article-title":"Immunotherapy delivered by Blinatumomab improves survival in acute lymphoblastic leukaemia patients","volume":"101","author":"Topp MS","year":"2016","journal-title":"Haematologica."},{"key":"e_1_2_5_5_1","article-title":"Pharmacokinetics\/pharmacodynamics (PKPD) of blinatumomab in patients with relapsed\/refractory B\u2010precursor acute lymphoblastic leukemia (r\/r ALL)","author":"Zhu M","year":"2015","journal-title":"J Clin Oncol."},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-400515"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-552729"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/01621459.1958.10501452"},{"key":"e_1_2_5_9_1","first-page":"1","article-title":"Statistical methods in cancer research. 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