{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T05:40:42Z","timestamp":1757310042967,"version":"3.37.3"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T00:00:00Z","timestamp":1625443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"name":"Medical Association Scientific Research Foundation of Sichuan","award":["No. S17058"],"award-info":[{"award-number":["No. S17058"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"published-print":{"date-parts":[[2022,5]]},"DOI":"10.1007\/s10238-021-00739-3","type":"journal-article","created":{"date-parts":[[2021,7,5]],"date-time":"2021-07-05T11:03:02Z","timestamp":1625482982000},"page":"161-171","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Venetoclax alone or in combination with other regimens treatment achieve deep and sustained remission of relapsed\/refractory chronic lymphocytic leukemia: a meta-analysis"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3634-5097","authenticated-orcid":false,"given":"Xiao","family":"Tang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenrong","family":"Zou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanglu","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,5]]},"reference":[{"issue":"8","key":"739_CR1","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1056\/NEJMra041720","volume":"352","author":"N Chiorazzi","year":"2005","unstructured":"Chiorazzi N, Rai KR, Ferrarini M, et al. Chronic lymphocytic leukemia. N Engl J Med. 2005;352(8):804\u201315.","journal-title":"N Engl J Med"},{"issue":"20","key":"739_CR2","doi-asserted-by":"publisher","first-page":"3059","DOI":"10.1182\/blood-2014-06-583765","volume":"124","author":"CS Tam","year":"2014","unstructured":"Tam CS, O\u2019Brien S, Plunkett W, et al. Long-term results of first salvage treatment in CLL patients treated initially with FCR (fludarabine, cyclophosphamide, rituximab). Blood. 2014;124(20):3059\u201364.","journal-title":"Blood"},{"key":"739_CR3","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1182\/blood-2015-06-651125","volume":"127","author":"K Fischer","year":"2016","unstructured":"Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127:208\u201315.","journal-title":"Blood"},{"issue":"7","key":"739_CR4","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1038\/leu.2015.14","volume":"29","author":"V Goede","year":"2015","unstructured":"Goede V, Fischer K, Engelke A, et al. Obinutuzumab as frontline treatment of chronic lymphocytic leukemia: updated results of the CLL11 study. Leukemia. 2015;29(7):1602\u20134.","journal-title":"Leukemia"},{"key":"739_CR5","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ctrv.2016.12.007","volume":"53","author":"T Robak","year":"2017","unstructured":"Robak T, Stilgenbauer S, Tedeschi A, et al. Front-line treatment of CLL in the era of novel agents. Cancer Treat Rev. 2017;53:70\u20138.","journal-title":"Cancer Treat Rev"},{"issue":"20","key":"739_CR6","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1182\/blood.2019001750","volume":"134","author":"DM Stephens","year":"2019","unstructured":"Stephens DM. Venetoclax and obinutuzumab for frontline treatment of chronic lymphocytic leukemia. Blood. 2019;134(20):1691\u20136.","journal-title":"Blood"},{"issue":"2","key":"739_CR7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1200\/JCO.2016.68.2856","volume":"35","author":"Q Chen","year":"2017","unstructured":"Chen Q, Jain N, Ayer T, et al. Economic burden of chronic lymphocytic leukemia in the era of oral targeted therapies in the United States. J Clin Oncol. 2017;35(2):166\u201374.","journal-title":"J Clin Oncol"},{"issue":"5","key":"739_CR8","doi-asserted-by":"publisher","first-page":"874","DOI":"10.3324\/haematol.2017.182907","volume":"103","author":"AR Mato","year":"2018","unstructured":"Mato AR, Nabhan C, Thompson MC, et al. Toxicities and outcomes of 616 ibrutinib-treated patients in the United States: a real-world analysis. Haematologica. 2018;103(5):874\u20139.","journal-title":"Haematologica"},{"issue":"2","key":"739_CR9","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/nm.3048","volume":"19","author":"AJ Souers","year":"2013","unstructured":"Souers AJ, Leverson JD, Boghaert ER, et al. ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets. Nat Med. 2013;19(2):202\u20138.","journal-title":"Nat Med"},{"issue":"4","key":"739_CR10","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2217\/ijh-2020-0010","volume":"9","author":"S Molica","year":"2020","unstructured":"Molica S. Venetoclax: a real game changer in treatment of chronic lymphocytic leukemia. Int J Hematol Oncol. 2020;9(4):31.","journal-title":"Int J Hematol Oncol"},{"issue":"23","key":"739_CR11","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.1056\/NEJMoa1815281","volume":"380","author":"K Fischer","year":"2019","unstructured":"Fischer K, Al-Sawaf O, Bahlo J, et al. Venetoclax and obinutuzumab in patients with CLL and coexisting conditions. N Engl J Med. 2019;380(23):2225\u201336.","journal-title":"N Engl J Med"},{"issue":"2","key":"739_CR12","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/S1470-2045(17)30012-8","volume":"18","author":"JF Seymour","year":"2017","unstructured":"Seymour JF, Ma S, Brander DM, et al. Venetoclax plus rituximab in relapsed or refractory chronic lymphocytic leukaemia: a phase 1b study. Lancet Oncol. 2017;18(2):230\u201340.","journal-title":"Lancet Oncol"},{"issue":"7","key":"739_CR13","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1080\/17474086.2020.1775575","volume":"13","author":"V Milunovic","year":"2020","unstructured":"Milunovic V, Jakobac KM, Rogulj IM, et al. The fading star of obinutuzumab\u2013chlorambucil regimen in patients with comorbidities with chronic lymphocytic leukemia\u2014are we ready for chemo-free immunotherapy approach? Expert Rev Hematol. 2020;13(7):771\u20139.","journal-title":"Expert Rev Hematol"},{"issue":"4","key":"739_CR14","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1200\/JCO.18.01580","volume":"37","author":"AP Kater","year":"2019","unstructured":"Kater AP, Seymour JF, Hillmen P, et al. Fixed duration of venetoclax-rituximab in relapsed\/refractory chronic lymphocytic leukemia eradicates minimal residual disease and prolongs survival: post-treatment follow-up of the MURANO phase III study. J Clin Oncol. 2019;37(4):269\u201377.","journal-title":"J Clin Oncol"},{"issue":"12","key":"739_CR15","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1056\/NEJMoa1713976","volume":"378","author":"JF Seymour","year":"2018","unstructured":"Seymour JF, Kipps TJ, Eichhorst B, et al. Venetoclax-rituximab in relapsed or refractory chronic lymphocytic leukemia. N Engl J Med. 2018;378(12):1107\u201320.","journal-title":"N Engl J Med"},{"issue":"6","key":"739_CR16","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/S1470-2045(16)30019-5","volume":"17","author":"S Stilgenbauer","year":"2016","unstructured":"Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768\u201378.","journal-title":"Lancet Oncol"},{"issue":"1","key":"739_CR17","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/2046-4053-4-1","volume":"4","author":"D Moher","year":"2015","unstructured":"Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1.","journal-title":"Syst Rev"},{"issue":"9","key":"739_CR18","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1046\/j.1445-2197.2003.02748.x","volume":"73","author":"K Slim","year":"2003","unstructured":"Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg. 2003;73(9):712\u20136.","journal-title":"ANZ J Surg"},{"issue":"4","key":"739_CR19","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1111\/bjh.15802","volume":"185","author":"TA Eyre","year":"2019","unstructured":"Eyre TA, Kirkwood AA, Gohill S, et al. Efficacy of venetoclax monotherapy in patients with relapsed chronic lymphocytic leukaemia in the post-BCR inhibitor setting: a UK wide analysis. Br J Haematol. 2019;185(4):656\u201369.","journal-title":"Br J Haematol"},{"issue":"30","key":"739_CR20","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1200\/JCO.19.00894","volume":"37","author":"P Hillmen","year":"2019","unstructured":"Hillmen P, Rawstron AC, Brock K, et al. Ibrutinib plus venetoclax in relapsed\/refractory chronic lymphocytic leukemia: the CLARITY study. J Clin Oncol. 2019;37(30):2722\u20139.","journal-title":"J Clin Oncol"},{"issue":"26","key":"739_CR21","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.1182\/blood-2019-01-896290","volume":"133","author":"LW Flinn","year":"2019","unstructured":"Flinn LW, Gribben JG, Dyer MJS, et al. Phase 1b study of venetoclax-obinutuzumab in previously untreated and relapsed\/refractory chronic lymphocytic leukemia. Blood. 2019;133(26):2765\u201375.","journal-title":"Blood"},{"issue":"4","key":"739_CR22","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1056\/NEJMoa1513257","volume":"74","author":"AW Roberts","year":"2016","unstructured":"Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;74(4):311\u201322.","journal-title":"N Engl J Med"},{"issue":"1","key":"739_CR23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S1470-2045(17)30909-9","volume":"19","author":"JA Jones","year":"2018","unstructured":"Jones JA, Mato AR, Wierda WG, et al. Venetoclax for chronic lymphocytic leukaemia progressing after ibrutinib: an interim analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018;19(1):65\u201375.","journal-title":"Lancet Oncol"},{"issue":"15","key":"739_CR24","doi-asserted-by":"publisher","first-page":"1704","DOI":"10.1182\/blood-2017-06-788133","volume":"131","author":"S Coutre","year":"2018","unstructured":"Coutre S, Choi M, Furman RR, et al. Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy. Blood. 2018;131(15):1704\u201311.","journal-title":"Blood"},{"issue":"19","key":"739_CR25","doi-asserted-by":"publisher","first-page":"1973","DOI":"10.1200\/JCO.2017.76.6840","volume":"36","author":"S Stilgenbauer","year":"2018","unstructured":"Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax for patients with chronic lymphocytic leukemia with 17p deletion: results from the full population of a phase II pivotal trial. J Clin Oncol. 2018;36(19):1973\u201380.","journal-title":"J Clin Oncol"},{"issue":"9","key":"739_CR26","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/S1470-2045(18)30414-5","volume":"19","author":"P Cramer","year":"2018","unstructured":"Cramer P, Tresckow J, Bahlo J, et al. Bendamustine followed by obinutuzumab and venetoclax in chronic lymphocytic leukaemia (CLL2-BAG): primary endpoint analysis of a multicentre, open-label, phase 2 trial. Lancet Oncol. 2018;19(9):1215\u201328.","journal-title":"Lancet Oncol"},{"issue":"9","key":"739_CR27","doi-asserted-by":"publisher","first-page":"1511","DOI":"10.3324\/haematol.2018.193615","volume":"103","author":"AR Mato","year":"2018","unstructured":"Mato AR, Thompson M, Allan JN, et al. Real-world outcomes and management strategies for venetoclax-treated chronic lymphocytic leukemia patients in the United States. Haematologica. 2018;103(9):1511\u20137.","journal-title":"Haematologica"},{"issue":"5","key":"739_CR28","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s40262-016-0453-9","volume":"56","author":"KJ Freise","year":"2017","unstructured":"Freise KJ, Jones AK, Eckert D, et al. Impact of venetoclax exposure on clinical efficacy and safety in patients with relapsed or refractory chronic lymphocytic leukemia. Clin Pharmacokinet. 2017;56(5):515\u201323.","journal-title":"Clin Pharmacokinet"},{"issue":"8","key":"739_CR29","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1182\/blood.2020008608","volume":"137","author":"CU Niemann","year":"2021","unstructured":"Niemann CU, Levin MD, Dubois J, et al. Venetoclax and ibrutinib for patients with relapsed\/refractory chronic lymphocytic leukemia. Blood. 2021;137(8):1117\u201320.","journal-title":"Blood"},{"issue":"10","key":"739_CR30","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.1182\/bloodadvances.2019000180","volume":"3","author":"AR Mato","year":"2019","unstructured":"Mato AR, Roeker LE, Eyre TA, et al. A retrospective comparison of venetoclax alone or in combination with an anti-CD20 monoclonal antibody in R\/R CLL. Blood Adv. 2019;3(10):1568\u201373.","journal-title":"Blood Adv"},{"issue":"22","key":"739_CR31","doi-asserted-by":"publisher","first-page":"2095","DOI":"10.1056\/NEJMoa1900574","volume":"380","author":"N Jain","year":"2019","unstructured":"Jain N, Keating M, Thompson P, et al. Ibrutinib and venetoclax for first-line treatment of CLL. N Engl J Med. 2019;380(22):2095\u2013103.","journal-title":"N Engl J Med"},{"issue":"9747","key":"739_CR32","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/S0140-6736(10)61381-5","volume":"376","author":"M Hallek","year":"2010","unstructured":"Hallek M, Fischer K, Fingerle-Rowson G, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. Lancet. 2010;376(9747):1164\u201374.","journal-title":"Lancet"},{"issue":"11","key":"739_CR33","doi-asserted-by":"publisher","first-page":"3016","DOI":"10.1182\/blood-2010-08-304683","volume":"117","author":"XC Badoux","year":"2011","unstructured":"Badoux XC, Keating MJ, Wang XM, et al. Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL. Blood. 2011;117(11):3016\u201324.","journal-title":"Blood"},{"issue":"18","key":"739_CR34","doi-asserted-by":"publisher","first-page":"4070","DOI":"10.1200\/JCO.2005.12.516","volume":"23","author":"W Wierda","year":"2005","unstructured":"Wierda W, O\u2019Brien S, Wen S, et al. Chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab for relapsed and refractory chronic lymphocytic leukemia. J Clin Oncol. 2005;23(18):4070\u20138.","journal-title":"J Clin Oncol"},{"issue":"4","key":"739_CR35","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1002\/cam4.1337","volume":"7","author":"XJ Huang","year":"2018","unstructured":"Huang XJ, Qiu LG, Jin J, et al. Ibrutinib versus rituximab in relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma: a randomized, open-label phase 3 study. Cancer Med. 2018;7(4):1043\u201355.","journal-title":"Cancer Med"},{"issue":"25","key":"739_CR36","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.1182\/blood-2016-01-688796","volume":"127","author":"MA Anderson","year":"2016","unstructured":"Anderson MA, Deng J, Seymour JF. The BCL2 selective inhibitor venetoclax induces rapid onset apoptosis of CLL cells in patients via a TP53-independent mechanism. Blood. 2016;127(25):3215\u201324.","journal-title":"Blood"},{"issue":"9","key":"739_CR37","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.1182\/blood.V84.9.3148.3148","volume":"84","author":"E Wattel","year":"1994","unstructured":"Wattel E, Preudhomme C, Hecquet B, et al. p53 mutations are associated with resistance to chemotherapy and short survival in hematologic malignancies. Blood. 1994;84(9):3148\u201357.","journal-title":"Blood"},{"issue":"24","key":"739_CR38","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1182\/blood-2016-05-714162","volume":"128","author":"M Kwok","year":"2016","unstructured":"Kwok M, Rawstron AC, Varghese A, et al. Minimal residual disease is an independent predictor for 10-year survival in CLL. Blood. 2016;128(24):2770\u20133.","journal-title":"Blood"},{"issue":"5","key":"739_CR39","doi-asserted-by":"publisher","first-page":"873","DOI":"10.3324\/haematol.2013.099796","volume":"99","author":"R Santacruz","year":"2014","unstructured":"Santacruz R, Villamor N, Aymerich M, et al. The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy. Haematologica. 2014;99(5):873\u201380.","journal-title":"Haematologica"},{"issue":"24","key":"739_CR40","doi-asserted-by":"publisher","first-page":"3727","DOI":"10.1182\/blood-2013-11-538116","volume":"123","author":"P Strati","year":"2014","unstructured":"Strati P, Keating MJ, O\u2019Brien SM, et al. Eradication of bone marrow minimal residual disease may prompt early treatment discontinuation in CLL. Blood. 2014;123(24):3727\u201332.","journal-title":"Blood"},{"issue":"4","key":"739_CR41","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/s41375-018-0276-9","volume":"33","author":"G Fraser","year":"2019","unstructured":"Fraser G, Cramer P, Demirkan F, et al. Updated results from the phase 3 HELIOS study of ibrutinib, bendamustine, and rituximab in relapsed chronic lymphocytic leukemia\/small lymphocytic lymphoma. Leukemia Leukemia. 2019;33(4):969\u201380.","journal-title":"Leukemia Leukemia"},{"issue":"18","key":"739_CR42","doi-asserted-by":"publisher","first-page":"4371","DOI":"10.1158\/1078-0432.CCR-17-3761","volume":"24","author":"MS Davids","year":"2018","unstructured":"Davids MS, Hallek M, Wierda W, et al. Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed\/refractory chronic lymphocytic leukemia. Clin Cancer Res. 2018;24(18):4371\u20139.","journal-title":"Clin Cancer Res"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00739-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-021-00739-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-021-00739-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,16]],"date-time":"2022-05-16T18:20:48Z","timestamp":1652725248000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-021-00739-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,5]]},"references-count":42,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,5]]}},"alternative-id":["739"],"URL":"https:\/\/doi.org\/10.1007\/s10238-021-00739-3","relation":{},"ISSN":["1591-9528"],"issn-type":[{"type":"electronic","value":"1591-9528"}],"subject":[],"published":{"date-parts":[[2021,7,5]]},"assertion":[{"value":"8 March 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This article does not contain any studies with human participants or animals performed by any of the authors.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}