{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T23:19:38Z","timestamp":1791242378261,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T00:00:00Z","timestamp":1454976000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Public Health Service Grants from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services","award":["CA180794, CA180820, CA180790, CA180888, CA189953, CA189957, CA180821, CA180799, CA189830, CA180853, CA180791"],"award-info":[{"award-number":["CA180794, CA180820, CA180790, CA180888, CA189953, CA189957, CA180821, CA180799, CA189830, CA180853, CA180791"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:p>Chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL) patients requiring initial therapy are often older and frailer and unsuitable candidates for standard chemoimmunotherapy regimens. Shorter duration combination monoclonal antibody (mAb) therapy using alemtuzumab and rituximab has been shown to be effective and tolerable treatment for CLL. Standard dose anti\u2010CD20 mAb therapy causes loss of CD20 expression by surviving CLL cells, which can be minimized by decreasing the mAb dose. We report a randomized phase II clinical trial enrolling older (\u2265 65 years) patients (median age 76 years, <jats:italic>n<\/jats:italic>\u2009=\u200931) with treatment na\u00efve progressive CLL. Patients received 8\u201012 weeks of standard subcutaneous alemtuzumab with either intravenous standard (375 mg\/m<jats:sup>2<\/jats:sup> weekly)(<jats:italic>n<\/jats:italic>\u2009=\u200916) or low dose (20 mg\/m<jats:sup>2<\/jats:sup> 3x week)(<jats:italic>n<\/jats:italic>\u2009=\u200915) rituximab. This study was closed before full accrual because the manufacturer withdrew alemtuzumab for treatment of CLL. The overall response rate was 90% with an 45% complete response rate, median progression\u2010free survival of 17.9 months and no significant differences in outcome between the low and standard dose rituximab arms. The major toxicities were cytopenia and infection with one treatment fatality caused by progressive multifocal leukoencephalopathy but no other opportunistic infections. Combination mAb therapy was effective and tolerable treatment for older and frailer patients with progressive CLL, achieving a high rate of complete remissions. These data support the role of mAb in therapy for less fit CLL patients and the further study of low dose higher frequency anti\u2010CD20 mAb therapy as a potentially more effective use of anti\u2010CD20 mAb in the treatment of CLL. Am. J. Hematol. 91:308\u2013312, 2016. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/ajh.24265","type":"journal-article","created":{"date-parts":[[2015,12,11]],"date-time":"2015-12-11T00:57:08Z","timestamp":1449795428000},"page":"308-312","source":"Crossref","is-referenced-by-count":12,"title":["A phase II randomized trial comparing standard and low dose rituximab combined with alemtuzumab as initial treatment of progressive chronic lymphocytic leukemia in older patients: a trial of the ECOG\u2010ACRIN cancer research group (E1908)"],"prefix":"10.1002","volume":"91","author":[{"given":"Clive S.","family":"Zent","sequence":"first","affiliation":[{"name":"University of Rochester Medical Center, Rochester, New York (Current Location) Mayo Clinic Rochester Minnesota (Former Location)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Victoria Wang","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute \u2013 ECOG\u2010ACRIN Biostatistics Center Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhett P.","family":"Ketterling","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Curtis A.","family":"Hanson","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward N.","family":"Libby","sequence":"additional","affiliation":[{"name":"Seattle Cancer Care Alliance, Seattle, Washington (Current Location) University of New Mexico Cancer Center Albuquerque NM"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline C.","family":"Barrientos","sequence":"additional","affiliation":[{"name":"North Shore\u2010LIJ Health System NCORP Manhasset New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy G.","family":"Call","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie E.","family":"Chang","sequence":"additional","affiliation":[{"name":"University of Wisconsin Madison Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane J.","family":"Liu","sequence":"additional","affiliation":[{"name":"Illinois CancerCare Peoria Illinois"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro R.","family":"Calvo","sequence":"additional","affiliation":[{"name":"Kettering Health Network Kettering Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hillard M.","family":"Lazarus","sequence":"additional","affiliation":[{"name":"Case Western Reserve University Cleveland Ohio"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob M.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Rambam Medical Center Haifa Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selina M.","family":"Luger","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Litzow","sequence":"additional","affiliation":[{"name":"Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin S.","family":"Tallman","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center, New York, New York (Current Location) Northwestern University School of Medicine Chicago Illinois (Former Location)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,2,9]]},"reference":[{"key":"e_1_2_6_2_1","unstructured":"HowladerN NooneA KrapchoM et al. SEER Cancer Statistics Review 1975\u20102012. National Cancer Institute Bethesda MD. Available at:http:\/\/seer.cancer.gov\/csr\/1975_2012\/;2015. Accessed November 2015."},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.12.051"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61381-5"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.114.092684"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2012.02.011"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-07-1952"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190412331286096"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23824"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2012.717276"},{"key":"e_1_2_6_11_1","first-page":"1","article-title":"Phase II study of alemtuzumab\u2010rituximab therapy in previously untreated patients with chronic lymphocytic leukemia: short\u2010 and long\u2010term outcomes","author":"Frankfurt O","year":"2014","journal-title":"Leuk Lymphoma"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2015.1016932"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7435"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.012484"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.23737"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V87.12.4990.bloodjournal87124990"},{"key":"e_1_2_6_17_1","first-page":"127","volume-title":"Tumours of Haematopoietic and Lymphoid Tissues","author":"Muller\u2010Hermelink HK","year":"2001"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(74)90015-0"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21979"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.608446"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2014.05.007"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2013-201781"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-01-0159"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.12.9098"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-008-0566-9"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-02-203075"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2010.01.009"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1313984"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60027-7"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.07.009"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.5.3280"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2600"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103693"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302954"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.24265","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.24265","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T12:26:03Z","timestamp":1695471963000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.24265"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,9]]},"references-count":34,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["10.1002\/ajh.24265"],"URL":"https:\/\/doi.org\/10.1002\/ajh.24265","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,9]]}}}