{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T14:45:10Z","timestamp":1761489910703},"reference-count":100,"publisher":"Elsevier BV","issue":"2","license":[{"start":{"date-parts":[[2016,4,1]],"date-time":"2016-04-01T00:00:00Z","timestamp":1459468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Seminars in Oncology"],"published-print":{"date-parts":[[2016,4]]},"DOI":"10.1053\/j.seminoncol.2016.02.005","type":"journal-article","created":{"date-parts":[[2016,2,9]],"date-time":"2016-02-09T07:17:46Z","timestamp":1455002266000},"page":"241-250","source":"Crossref","is-referenced-by-count":10,"title":["Initial therapy of chronic lymphocytic leukemia"],"prefix":"10.1053","volume":"43","author":[{"given":"Barbara","family":"Eichhorst","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Cramer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Hallek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1053\/j.seminoncol.2016.02.005_bib1","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1002\/1097-0142(195605\/06)9:3<512::AID-CNCR2820090312>3.0.CO;2-O","article-title":"Early experience with p-(N, N-di-2-chloroethyl)-aminophenylbutyric acid (CB 1348), a new chemotherapeutic agent effective in the treatment of chronic lymphocytic leukemia","volume":"9","author":"Altman","year":"1956","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/1097-0142(197303)31:3<502::AID-CNCR2820310303>3.0.CO;2-7","article-title":"Chlorambucil vs. combined chlorambucil-corticosteroid therapy in chronic lymphocytic leukemia","volume":"31","author":"Han","year":"1973","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib3","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/1097-0142(197402)33:2<555::AID-CNCR2820330234>3.0.CO;2-I","article-title":"Proceedings: Bi-weekly chlorambucil treatment of chronic lymphocytic leukemia","volume":"33","author":"Knospe","year":"1974","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib4","first-page":"433","article-title":"CHOP versus prednisolone + chlorambucil in chronic lymphocytic leukemia (CLL): preliminary results of a randomized multicenter study","volume":"30","author":"Hansen","year":"1988","journal-title":"Nouv Rev Fr Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib5","doi-asserted-by":"crossref","first-page":"2369","DOI":"10.1002\/1097-0142(19851115)56:10<2369::AID-CNCR2820561004>3.0.CO;2-N","article-title":"Treatment of chronic lymphocytic leukemia in advanced stages. A randomized trial comparing chlorambucil plus prednisone versus cyclophosphamide, vincristine, and prednisone","volume":"56","author":"Montserrat","year":"1985","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib6","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1200\/JCO.1991.9.5.770","article-title":"Comparison of chlorambucil and prednisone versus cyclophosphamide, vincristine, and prednisone as initial treatment for chronic lymphocytic leukemia: long-term follow-up of an Eastern Cooperative Oncology Group randomized clinical trial","volume":"9","author":"Raphael","year":"1991","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib7","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1200\/JCO.1991.9.1.44","article-title":"Fludarabine: a new agent with marked cytoreductive activity in untreated chronic lymphocytic leukemia","volume":"9","author":"Keating","year":"1991","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib8","doi-asserted-by":"crossref","first-page":"2878","DOI":"10.1182\/blood.V81.11.2878.2878","article-title":"Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent","volume":"81","author":"Keating","year":"1993","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib9","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1016\/S0140-6736(96)91681-5","article-title":"Multicentre prospective randomised trial of fludarabine versus cyclophosphamide, doxorubicin, and prednisone (CAP) for treatment of advanced-stage chronic lymphocytic leukaemia. The French Cooperative Group on CLL","volume":"347","author":"FrenchCooperativeGrouponCLL","year":"1996","journal-title":"Lancet"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib10","first-page":"2723","article-title":"Cladribine with prednisone versus chlorambucil with prednisone as first-line therapy in chronic lymphocytic leukemia: report of a prospective, randomized, multicenter trial","volume":"96","author":"Robak","year":"2000","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib11","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.1056\/NEJM200012143432402","article-title":"Fludarabine compared with chlorambucil as primary therapy for chronic lymphocytic leukemia","volume":"343","author":"Rai","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib12","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1182\/blood-2005-06-2395","article-title":"Fludarabine plus cyclophosphamide versus fludarabine alone in first-line therapy of younger patients with chronic lymphocytic leukemia","volume":"107","author":"Eichhorst","year":"2006","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib13","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1200\/JCO.2006.08.0762","article-title":"Phase III trial of fludarabine plus cyclophosphamide compared with fludarabine for patients with previously untreated chronic lymphocytic leukemia: US Intergroup Trial E2997","volume":"25","author":"Flinn","year":"2007","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib14","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/S0140-6736(07)61125-8","article-title":"Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial","volume":"370","author":"Catovsky","year":"2007","journal-title":"Lancet"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib15","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1182\/blood-2005-12-4828","volume":"108","author":"Robak","year":"2006","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib16","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1056\/NEJM199805213382104","article-title":"Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia","volume":"338","author":"Dighiero","year":"1998","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib17","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/BF01714955","article-title":"Treatment of early stage-B chronic lymphocytic leukemia with alpha-2b interferon after chlorambucil reduction of the tumoral mass","volume":"63","author":"Montserrat","year":"1991","journal-title":"Ann Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib18","doi-asserted-by":"crossref","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","article-title":"Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines","volume":"111","author":"Hallek","year":"2008","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib19","unstructured":"Howlader NNA, Krapcho M, Garshell J, (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute. Bethesda, MD. http:\/\/seercancergov\/csr\/1975_2011\/, based on November 2013 SEER data submission, posted to the SEER web site, April 2014 2014."},{"key":"10.1053\/j.seminoncol.2016.02.005_bib20","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1111\/j.1532-5415.1968.tb02103.x","article-title":"Cumulative illness rating scale","volume":"16","author":"Linn","year":"1968","journal-title":"J Am Geriatr Soc"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib21","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/0165-1781(92)90005-N","article-title":"Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale","volume":"41","author":"Miller","year":"1992","journal-title":"Psychiatry Res"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib22","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/0895-4356(94)90129-5","article-title":"Validation of a combined comorbidity index","volume":"47","author":"Charlson","year":"1994","journal-title":"J Clin Epidemiol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib23","doi-asserted-by":"crossref","first-page":"2123","DOI":"10.1002\/(SICI)1097-0142(19980601)82:11<2123::AID-CNCR6>3.0.CO;2-W","article-title":"Comorbidity and age as predictors of risk for early mortality of male and female colon carcinoma patients: a population-based study","volume":"82","author":"Yancik","year":"1998","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib24","doi-asserted-by":"crossref","first-page":"e437","DOI":"10.1016\/S1470-2045(12)70259-0","article-title":"Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review","volume":"13","author":"Hamaker","year":"2012","journal-title":"Lancet Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib25","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.leukres.2013.12.018","article-title":"The relevance of a geriatric assessment for elderly patients with a haematological malignancy\u2014a systematic review","volume":"38","author":"Hamaker","year":"2014","journal-title":"Leuk Res"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib26","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1200\/JCO.1998.16.4.1582","article-title":"Comorbidity and functional status are independent in older cancer patients","volume":"16","author":"Extermann","year":"1998","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib27","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S1040-8428(00)00090-1","article-title":"Measurement and impact of comorbidity in older cancer patients","volume":"35","author":"Extermann","year":"2000","journal-title":"Crit Rev Oncol Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib28","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1634\/theoncologist.5-3-224","article-title":"Management of cancer in the older person: a practical approach","volume":"5","author":"Balducci","year":"2000","journal-title":"Oncologist"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib29","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1056\/NEJM200012283432602","article-title":"Genomic aberrations and survival in chronic lymphocytic leukemia","volume":"343","author":"D\u00f6hner","year":"2000","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib30","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1158\/1078-0432.CCR-08-1630","article-title":"The prognostic value of TP53 mutations in chronic lymphocytic leukemia is independent of Del17p13: implications for overall survival and chemorefractoriness","volume":"15","author":"Rossi","year":"2009","journal-title":"Clin Cancer Res"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib31","doi-asserted-by":"crossref","first-page":"4473","DOI":"10.1200\/JCO.2009.27.8762","article-title":"TP53 mutation and survival in chronic lymphocytic leukemia","volume":"28","author":"Zenz","year":"2010","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib32","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/leu.2012.25","article-title":"ERIC recommendations on TP53 mutation analysis in chronic lymphocytic leukemia","volume":"26","author":"Pospisilova","year":"2012","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib33","doi-asserted-by":"crossref","first-page":"3247","DOI":"10.1182\/blood-2014-01-546150","article-title":"Gene mutations and treatment outcome in chronic lymphocytic leukemia: results from the CLL8 trial","volume":"123","author":"Stilgenbauer","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib34","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1038\/leu.2012.25","article-title":"ERIC recommendations on TP53 mutation analysis in Chronic Lymphocytic Leukemia","volume":"26","author":"Pospisilova","year":"2012","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib35","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.1056\/NEJMoa1109016","article-title":"SF3B1 and other novel cancer genes in chronic lymphocytic leukemia","volume":"365","author":"Wang","year":"2011","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib36","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.cell.2013.01.019","article-title":"Evolution and impact of subclonal mutations in chronic lymphocytic leukemia","volume":"152","author":"Landau","year":"2013","journal-title":"Cell"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib37","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/leu.2014.196","article-title":"Recurrent mutations refine prognosis in chronic lymphocytic leukemia","volume":"29","author":"Baliakas","year":"2014","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib38","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1046\/j.1365-2141.2001.03014.x","article-title":"Synergism between fludarabine and rituximab revealed in a follicular lymphoma cell line resistant to the cytotoxic activity of either drug alone","volume":"114","author":"Di Gaetano","year":"2001","journal-title":"British journal of haematology"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib39","doi-asserted-by":"crossref","first-page":"3115","DOI":"10.1182\/blood-2002-03-0972","article-title":"Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia","volume":"100","author":"Schulz","year":"2002","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib40","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1182\/blood-2002-04-1258","article-title":"Randomized phase 2 study of fludarabine with concurrent versus sequential treatment with rituximab in symptomatic, untreated patients with B-cell chronic lymphocytic leukemia: results from Cancer and Leukemia Group B 9712 (CALGB 9712)","volume":"101","author":"Byrd","year":"2003","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib41","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1182\/blood-2004-03-0796","article-title":"Addition of rituximab to fludarabine may prolong progression-free survival and overall survival in patients with previously untreated chronic lymphocytic leukemia: an updated retrospective comparative analysis of CALGB 9712 and CALGB 9011","volume":"105","author":"Byrd","year":"2005","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib42","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1200\/JCO.2010.31.1811","article-title":"Chemoimmunotherapy with fludarabine and rituximab produces extended overall survival and progression-free survival in chronic lymphocytic leukemia: long-term follow-up of CALGB study 9712","volume":"29","author":"Woyach","year":"2011","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib43","doi-asserted-by":"crossref","first-page":"4079","DOI":"10.1200\/JCO.2005.12.051","article-title":"Early results of a chemoimmunotherapy regimen of fludarabine, cyclophosphamide, and rituximab as initial therapy for chronic lymphocytic leukemia","volume":"23","author":"Keating","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib44","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1182\/blood-2008-02-140582","article-title":"Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia","volume":"112","author":"Tam","year":"2008","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib45","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/S0140-6736(10)61381-5","article-title":"Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia: a randomised, open-label, phase III trial","volume":"376","author":"Hallek","year":"2010","journal-title":"Lancet"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib46","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1200\/JCO.2011.36.9348","article-title":"Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial","volume":"30","author":"Bottcher","year":"2012","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib47","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1182\/blood-2015-06-651125","volume":"127","author":"Fischer","year":"2016","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib48","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1158\/1078-0432.CCR-07-1371","article-title":"Fludarabine, cyclophosphamide, and mitoxantrone as initial therapy of chronic lymphocytic leukemia: high response rate and disease eradication","volume":"14","author":"Bosch","year":"2008","journal-title":"Clin Cancer Res"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib49","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1038\/leu.2010.199","article-title":"A phase I study of lenalidomide in combination with fludarabine and rituximab in previously untreated CLL\/SLL","volume":"24","author":"Brown","year":"2010","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib50","doi-asserted-by":"crossref","DOI":"10.1182\/blood.V122.21.4164.4164","article-title":"Lenalidomide\/rituximab maintenance after induction with fludarabine\/rituximab in combination with escalating doses of lenalidomide in previously untreated chronic lymphocytic leukemia (CLL): the Revlirit CLL5 AGMT phase I\/II study, final results","volume":"122","author":"Egle","year":"2013","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib51","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/ajh.23983","article-title":"Reduced-dose fludarabine, cyclophosphamide and rituximab (FCR-Lite) plus lenalidomide, followed by lenalidomide consolidation\/maintenance, in previously untreated chronic lymphocytic leukemia","volume":"90","author":"Mato","year":"2015","journal-title":"Am J Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib52","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1600-0609.2007.00889.x","article-title":"Rituximab plus cladribine with or without cyclophosphamide in patients with relapsed or refractory chronic lymphocytic leukemia","volume":"79","author":"Robak","year":"2007","journal-title":"Eur J Haematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib53","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1182\/blood-2006-07-033274","article-title":"Combination chemoimmunotherapy with pentostatin, cyclophosphamide, and rituximab shows significant clinical activity with low accompanying toxicity in previously untreated B chronic lymphocytic leukemia","volume":"109","author":"Kay","year":"2007","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib54","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1007\/s10637-011-9737-y","article-title":"A phase III trial of fludarabine, cyclophosphamide, and rituximab vs. pentostatin, cyclophosphamide, and rituximab in B-cell chronic lymphocytic leukemia","volume":"30","author":"Reynolds","year":"2012","journal-title":"Invest New Drugs"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib55","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/modpathol.2011.158","article-title":"Therapy-related myeloid neoplasms following fludarabine, cyclophosphamide, and rituximab (FCR) treatment in patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma","volume":"25","author":"Zhou","year":"2012","journal-title":"Mod Pathol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib56","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3109\/10428194.2011.605188","article-title":"Oral fludarabine and rituximab as initial therapy for chronic lymphocytic leukemia or small lymphocytic lymphoma: population-based experience matches clinical trials","volume":"53","author":"Gerrie","year":"2012","journal-title":"Leuk Lymphoma"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib57","doi-asserted-by":"crossref","first-page":"6450","DOI":"10.1182\/blood-2010-12-323980","article-title":"Chemoimmunotherapy with O-FC in previously untreated patients with chronic lymphocytic leukemia","volume":"117","author":"Wierda","year":"2011","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib58","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1002\/cncr.28292","article-title":"Ofatumumab-based chemoimmunotherapy is effective and well tolerated in patients with previously untreated chronic lymphocytic leukemia (CLL)","volume":"119","author":"Shanafelt","year":"2013","journal-title":"Cancer"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib59","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S1470-2045(11)70242-X","article-title":"Fludarabine plus alemtuzumab versus fludarabine alone in patients with previously treated chronic lymphocytic leukaemia: a randomised phase 3 trial","volume":"12","author":"Elter","year":"2011","journal-title":"Lancet Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib60","doi-asserted-by":"crossref","first-page":"2549","DOI":"10.1038\/leu.2012.129","article-title":"Fludarabine and cyclophosphamide in combination with alemtuzumab in patients with primary high-risk, relapsed or refractory chronic lymphocytic leukemia","volume":"26","author":"Elter","year":"2012","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib61","doi-asserted-by":"crossref","first-page":"5104","DOI":"10.1182\/blood-2011-07-365437","article-title":"Excess mortality after treatment with fludarabine and cyclophosphamide in combination with alemtuzumab in previously untreated patients with chronic lymphocytic leukemia in a randomized phase 3 trial","volume":"119","author":"Lepretre","year":"2012","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib62","doi-asserted-by":"crossref","first-page":"3255","DOI":"10.1182\/blood-2014-01-547737","article-title":"Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL","volume":"123","author":"Geisler","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib63","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1182\/blood-2011-01-329177","article-title":"Frontline chemoimmunotherapy with fludarabine, cyclophosphamide, alemtuzumab, and rituximab for high-risk chronic lymphocytic leukemia","volume":"118","author":"Parikh","year":"2011","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib64","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1200\/JCO.2011.39.2688","article-title":"Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group","author":"Fischer","year":"2012","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib65","first-page":"124","author":"Eichhorst","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib66","unstructured":"Offner F, Panagiotides P, Afanasyev B, et al. Ofatumumab and bendamustine combination therapy in patients with untreated and relapsed chronic lymphocytic leukemia: initial results of the phase II study OMB115991. XV iwCLL Meeting Abstracts 2013:429."},{"key":"10.1053\/j.seminoncol.2016.02.005_bib67","doi-asserted-by":"crossref","first-page":"3382","DOI":"10.1182\/blood-2009-02-206185","article-title":"First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia","volume":"114","author":"Eichhorst","year":"2009","journal-title":"Blood"},{"issue":"Suppl 1","key":"10.1053\/j.seminoncol.2016.02.005_bib68","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1016\/j.clml.2011.02.006","article-title":"Chlorambucil\u2014still not bad: a reappraisal","volume":"11","author":"Catovsky","year":"2011","journal-title":"Clin Lymph Myeloma Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib69","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1200\/JCO.2011.41.5646","article-title":"Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential Cancer and Leukemia Group B studies","volume":"31","author":"Woyach","year":"2013","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib70","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1200\/JCO.2013.49.6547","article-title":"Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: final analysis of an open-label phase II study","volume":"32","author":"Hillmen","year":"2014","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib71","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1002\/ajh.23668","article-title":"Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients","volume":"89","author":"Foa","year":"2014","journal-title":"Am J Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib72","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2141.2010.08428.x","article-title":"Comparison of the in vitro effects of the anti-CD20 antibodies rituximab and GA101 on chronic lymphocytic leukaemia cells","volume":"152","author":"Patz","year":"2011","journal-title":"Br J Haematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib73","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1158\/1535-7163.MCT-10-0385","article-title":"Preclinical studies on the mechanism of action and the anti-lymphoma activity of the novel anti-CD20 antibody GA101","volume":"10","author":"Dalle","year":"2011","journal-title":"Mol Cancer Ther"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib74","doi-asserted-by":"crossref","first-page":"4393","DOI":"10.1182\/blood-2009-06-225979","article-title":"Increasing the efficacy of CD20 antibody therapy through the engineering of a new type II anti-CD20 antibody with enhanced direct and immune effector cell-mediated B-cell cytotoxicity","volume":"115","author":"Mossner","year":"2010","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib75","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1056\/NEJMoa1313984","article-title":"Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions","volume":"370","author":"Goede","year":"2014","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib76","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/leu.2015.14","article-title":"Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study","volume":"29","author":"Goede","year":"2015","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib77","doi-asserted-by":"crossref","first-page":"1873","DOI":"10.1016\/S0140-6736(15)60027-7","article-title":"Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial","volume":"385","author":"Hillmen","year":"2015","journal-title":"Lancet"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib78","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1200\/JCO.2008.17.2619","article-title":"Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia","volume":"27","author":"Foon","year":"2009","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib79","doi-asserted-by":"crossref","first-page":"3184","DOI":"10.1182\/blood-2012-01-408047","article-title":"Long-term results of chemoimmunotherapy with low-dose fludarabine, cyclophosphamide and high-dose rituximab as initial treatment for patients with chronic lymphocytic leukemia","volume":"119","author":"Foon","year":"2012","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib80","article-title":"A randomised dose de-escalation study of oral fludarabine, \u00b1oral cyclophosphamide and intravenous rituximab as first-line therapy of fit patients with chronic lymphocytic leukaemia (CLL) aged \u226565 years: final analysis of response and toxicity","volume":"124","author":"Mulligan","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib81","first-page":"1","article-title":"Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia","volume":"28","author":"Dartigeas","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib82","first-page":"124","article-title":"Low-dose FCR is a safe and effective treatment option for elderly\/comorbid patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma. Updated Results of Project Q-Lite By Czech CLL Study Group","author":"Smolej","year":"2014","journal-title":"Blood"},{"issue":"Suppl 1","key":"10.1053\/j.seminoncol.2016.02.005_bib83","article-title":"Rituximab in combination with bendamustine or chlorambucil for the treatment of chronic lymphocytic leukaemia: primary results from the randomised phase IIIb MABLE study","volume":"56","author":"Michallet","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib84","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1007\/s00277-014-2048-6","article-title":"Treatment practice in the elderly patient with chronic lymphocytic leukemia-analysis of the combined SEER and Medicare database","volume":"93","author":"Satram-Hoang","year":"2014","journal-title":"Ann Hematol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib85","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1038\/leu.2009.133","article-title":"Rituximab in combination with high-dose methylprednisolone for the treatment of chronic lymphocytic leukemia","volume":"23","author":"Castro","year":"2009","journal-title":"Leukemia"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib86","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1182\/blood-2011-03-339077","article-title":"Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia","volume":"118","author":"Badoux","year":"2011","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib87","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1182\/blood-2013-04-495341","article-title":"Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia","volume":"122","author":"Strati","year":"2013","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib88","doi-asserted-by":"crossref","first-page":"2067","DOI":"10.1200\/JCO.2013.51.5890","article-title":"Lenalidomide and rituximab for the initial treatment of patients with chronic lymphocytic leukemia: a multicenter clinical-translational study from the chronic lymphocytic leukemia research consortium","volume":"32","author":"James","year":"2014","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib89","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/S1470-2045(13)70513-8","article-title":"Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b\/2 trial","volume":"15","author":"O\u2019Brien","year":"2014","journal-title":"Lancet Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib90","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1056\/NEJMoa1509388","article-title":"Ibrutinib as initial therapy for patients with cronic lmphocytic lukemia","volume":"373","author":"Burger","year":"2015","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib91","first-page":"2188","article-title":"Ibrutinib inhibits B-cell receptor and NF-kappaB signaling and reduces tumor proliferation in tissue-resident cells of patients with chronic lymphocytic leukemia","volume":"28","author":"Herman","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib92","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa1215637","article-title":"Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia","volume":"369","author":"Byrd","year":"2013","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib93","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/S1470-2045(14)70335-3","article-title":"Safety and activity of ibrutinib plus rituximab for patients with high-risk chronic lymphocytic leukaemia: a single-arm, phase 2 study","volume":"15","author":"Burger","year":"2014","journal-title":"Lancet Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib94","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa1315226","article-title":"Idelalisib and rituximab in relapsed chronic lymphocytic leukemia","volume":"370","author":"Furman","year":"2014","journal-title":"N Engl J Med"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib95","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1182\/blood-2013-11-535047","article-title":"Idelalisib, an inhibitor of phosphatidylinositol 3 kinase p110delta, for relapsed\/refractory chronic lymphocytic leukemia","volume":"123","author":"Brown","year":"2014","journal-title":"Blood"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib96","doi-asserted-by":"crossref","unstructured":"Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood 2015;125:2497-506","DOI":"10.1182\/blood-2014-10-606038"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib97","doi-asserted-by":"crossref","unstructured":"Dreger P, Schetelig J, Andersen N, et al. Managing high-risk chronic lymphocytic leukemia during transition to a new treatment era: stem cell transplantation or novel agents? Blood 2014;124:3841-9","DOI":"10.1182\/blood-2014-07-586826"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib98","doi-asserted-by":"crossref","first-page":"1756","DOI":"10.1200\/JCO.2009.26.4556","article-title":"Rituximab plus fludarabine and cyclophosphamide prolongs progression-free survival compared with fludarabine and cyclophosphamide alone in previously treated chronic lymphocytic leukemia","volume":"28","author":"Robak","year":"2010","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib99","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1200\/JCO.2005.04.021","article-title":"Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival","volume":"23","author":"Moreton","year":"2005","journal-title":"J Clin Oncol"},{"key":"10.1053\/j.seminoncol.2016.02.005_bib100","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1182\/blood-2013-09-527853","article-title":"Prolonged lymphocytosis during ibrutinib therapy is associated with distinct molecular characteristics and does not indicate a suboptimal response to therapy","volume":"123","author":"Woyach","year":"2014","journal-title":"Blood"}],"container-title":["Seminars in Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0093775416000117?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0093775416000117?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T04:29:01Z","timestamp":1600144141000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0093775416000117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":100,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["S0093775416000117"],"URL":"https:\/\/doi.org\/10.1053\/j.seminoncol.2016.02.005","relation":{},"ISSN":["0093-7754"],"issn-type":[{"value":"0093-7754","type":"print"}],"subject":[],"published":{"date-parts":[[2016,4]]}}}