{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:16:19Z","timestamp":1790766979434,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T00:00:00Z","timestamp":1606953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2021,4,15]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>CXCR4 mediates the retention and survival of acute myelogenous leukemia blasts in bone marrow and contributes to their resistance to chemotherapy. The authors evaluated a combination of the high\u2010affinity CXCR4 antagonist BL\u20108040 with high\u2010dose cytarabine (HiDAC) chemotherapy in a phase 2a study of patients with relapsed and refractory AML.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Forty\u2010two patients received treatment with BL\u20108040 monotherapy for 2 days followed by a combination of BL\u20108040 with HiDAC for 5 days. Six escalating BL\u20108040 dose levels were investigated (0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 mg\/kg), and 1.5 mg\/kg was selected as the dose for the expansion phase (n = 23).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>BL\u20108040 in combination with HiDAC was safe and well tolerated at all dose levels. Clinical response was observed with BL\u20108040 doses \u22651.0 mg\/kg. The composite response rate (complete remissions plus complete remissions with incomplete hematologic recovery of platelets or neutrophils) was 29% (12 of 42) in all patients and 39% (9 of 23) in the 1.5\u2010mg\/kg phase. The median overall survival was 8.4 months for all patients, 10.8 months in the 1.5\u2010mg\/kg phase, and 21.8 months for responding patients in the 1.5\u2010mg\/kg cohort. Two days of BL\u20108040 monotherapy triggered the mobilization of blasts into peripheral blood, with significantly higher mean fold\u2010changes in responders versus nonresponders. This was accompanied by a decrease in bone marrow blasts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current results demonstrate the efficacy of CXCR4 targeting with BL\u20108040 and support continued clinical development in acute myelogenous leukemia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.33338","type":"journal-article","created":{"date-parts":[[2020,12,3]],"date-time":"2020-12-03T12:34:05Z","timestamp":1606998845000},"page":"1246-1259","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["BL\u20108040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed\/refractory acute myelogenous leukemia: An open\u2010label safety and efficacy phase 2a study"],"prefix":"10.1002","volume":"127","author":[{"given":"Gautam","family":"Borthakur","sequence":"first","affiliation":[{"name":"Department of Leukemia The University of Texas MD Anderson Cancer Center Houston Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yishai","family":"Ofran","sequence":"additional","affiliation":[{"name":"Laboratory of genetic and immunology of Leukemia Rambam Medical Center Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Tallman","sequence":"additional","affiliation":[{"name":"Memorial Sloan\u2010Kettering Cancer Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1673-1708","authenticated-orcid":false,"given":"James","family":"Foran","sequence":"additional","affiliation":[{"name":"Cancer center, Bone Marrow Transplant Program, Hematology Mayo Clinic Jacksonville Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey L.","family":"Uy","sequence":"additional","affiliation":[{"name":"Oncology Division Bone Marrow Transplantation &amp; Leukemia Washington University School of Medicine St Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"DiPersio","sequence":"additional","affiliation":[{"name":"Oncology Division Bone Marrow Transplantation &amp; Leukemia Washington University School of Medicine St Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret M.","family":"Showel","sequence":"additional","affiliation":[{"name":"Johns Hopkins School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8782-6160","authenticated-orcid":false,"given":"Avichai","family":"Shimoni","sequence":"additional","affiliation":[{"name":"Division of Hematology Chaim Sheba Medical Center Ramat\u2010Gan Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnon","family":"Nagler","sequence":"additional","affiliation":[{"name":"Division of Hematology Chaim Sheba Medical Center Ramat\u2010Gan Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Shaare Zedek Medical Center Jerusalem Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica K.","family":"Altman","sequence":"additional","affiliation":[{"name":"Robert H. 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