{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,27]],"date-time":"2025-09-27T03:33:48Z","timestamp":1758944028065,"version":"3.37.3"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T00:00:00Z","timestamp":1337299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004329","name":"Genzyme","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004329","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NCI Cancer Center","award":["2P30 CA06973-47"],"award-info":[{"award-number":["2P30 CA06973-47"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2012,7]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The prognosis of patients with relapsed and refractory acute leukaemia (<jats:styled-content style=\"fixed-case\">RRAL<\/jats:styled-content>) is very poor. Forty patients with <jats:styled-content style=\"fixed-case\">RRAL<\/jats:styled-content> were enroled [28 acute myeloid leukaemia (<jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content>), 12 acute lymphoblastic leukaemia (<jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>)] in this Phase 1 dose\u2010escalation trial of daily\u2010infused clofarabine (<jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>) followed by cyclophosphamide (<jats:styled-content style=\"fixed-case\">CY<\/jats:styled-content>) for four consecutive days (<jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CY<\/jats:styled-content>x4). The median age was 48\u00b75\u00a0years. The median number of prior regimens was 2 (range 1\u20135), and 6\/40 patients (15%) had prior allogeneic haematopoietic stem cell transplant. 28\/40 patients (70%) had adverse genetic features. 6\/40 patients (15%) died within 60\u00a0d of induction (two infections, four progressive disease). The average time to neutrophil recovery (absolute neutrophil count \u22650\u00b75\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/l was 34\u00a0d, (range, 17\u201378). The overall response rate (<jats:styled-content style=\"fixed-case\">ORR<\/jats:styled-content>) was 33% (13\/40), with seven complete remissions (18%), four complete remissions with incomplete recovery of blood counts (10%), and two partial remissions (5%). <jats:styled-content style=\"fixed-case\">ORR<\/jats:styled-content> was 25% (7\/28), and 50% (6\/12), for <jats:styled-content style=\"fixed-case\">AML<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content> respectively. Notably, the clinical responses were independent of dose level. 7\/17 patients (41%) exhibited <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>\u2010mediated enhancement of <jats:styled-content style=\"fixed-case\">CY<\/jats:styled-content>\u2010induced <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content>, which was associated with, but not necessary for, improved clinical outcomes. In summary, the <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CY<\/jats:styled-content>x4 regimen was well tolerated and had activity in patients with <jats:styled-content style=\"fixed-case\">RRAL<\/jats:styled-content>, especially relapsed <jats:styled-content style=\"fixed-case\">ALL<\/jats:styled-content>. Therefore, <jats:styled-content style=\"fixed-case\">CLO<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">CY<\/jats:styled-content>x4 can be considered a salvage therapy for adults with <jats:styled-content style=\"fixed-case\">RRAL<\/jats:styled-content>s, and warrants further investigations.<\/jats:p>","DOI":"10.1111\/j.1365-2141.2012.09142.x","type":"journal-article","created":{"date-parts":[[2012,5,18]],"date-time":"2012-05-18T09:35:12Z","timestamp":1337333712000},"page":"198-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Phase 1 dose\u2010escalation trial of clofarabine followed by escalating dose of fractionated cyclophosphamide in adults with relapsed or refractory acute leukaemias"],"prefix":"10.1111","volume":"158","author":[{"given":"Amer M.","family":"Zeidan","sequence":"first","affiliation":[{"name":"Division of Hematologic Malignancies Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca M.","family":"Ricklis","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hetty E.","family":"Carraway","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyun D.","family":"Yun","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacqueline M.","family":"Greer","sequence":"additional","affiliation":[{"name":"Division of Hematologic Malignancies Department of Oncology The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins  Baltimore MD USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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