{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:46:45Z","timestamp":1788788805248,"version":"build-2803163510"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T00:00:00Z","timestamp":1494806400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,5,15]],"date-time":"2017-05-15T00:00:00Z","timestamp":1494806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1038\/leu.2017.145","type":"journal-article","created":{"date-parts":[[2017,5,11]],"date-time":"2017-05-11T10:50:42Z","timestamp":1494499842000},"page":"2587-2593","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients"],"prefix":"10.1038","volume":"31","author":[{"given":"J","family":"Pan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J F","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B P","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X J","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y H","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y N","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z L","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y L","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S H","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P H","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D P","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C R","family":"Tong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,15]]},"reference":[{"key":"BFleu2017145_CR1","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1182\/blood.V126.23.3224.3224","volume":"126","author":"Zhao Yan-Li","year":"2015","unstructured":"Yan-Li Zhao, Tong Wu, Yue Lu, Xing-Yu Cao, De-Yan Liu, Min Xiong et al. Improved outcomes of haploidentical blood and marrow transplantation in hematologic malignancies: a single center study of 514 cases. Blood 2015; 126: 3224.","journal-title":"Blood"},{"key":"BFleu2017145_CR2","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/bmt.2015.103","volume":"50","author":"MA Pulsipher","year":"2015","unstructured":"Pulsipher MA, Langholz B, Wall DA, Schultz KR, Bunin N, Carroll W et al. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested? Bone Marrow Transplant 2015; 50: 1173\u20131179.","journal-title":"Bone Marrow Transplant"},{"key":"BFleu2017145_CR3","doi-asserted-by":"publisher","first-page":"10024","DOI":"10.1073\/pnas.86.24.10024","volume":"86","author":"G Gross","year":"1989","unstructured":"Gross G, Waks T, Eshhar Z . Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci USA 1989; 86: 10024\u201310028.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFleu2017145_CR4","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1016\/0092-8674(91)90314-O","volume":"64","author":"BA Irving","year":"1991","unstructured":"Irving BA, Weiss A . The cytoplasmic domain of the T cell receptor \u03b6 chain is sufficient to couple to receptor-associated signal transduction pathways. Cell 1991; 64: 891\u2013901.","journal-title":"Cell"},{"key":"BFleu2017145_CR5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1182\/blood.V71.1.13.13","volume":"71","author":"FM Uckun","year":"1988","unstructured":"Uckun FM, Jaszcz W, Ambrus JL, Fauci AS, Gajl-Peczalska K, Song CW et al. Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins. Blood 1988; 71: 13\u201329.","journal-title":"Blood"},{"key":"BFleu2017145_CR6","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1056\/NEJMoa1103849","volume":"365","author":"DL Porter","year":"2011","unstructured":"Porter DL, Levine BL, Kalos M, Bagg A, June CH . Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med 2011; 365: 725\u2013733.","journal-title":"N Engl J Med"},{"key":"BFleu2017145_CR7","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/j.coi.2009.02.009","volume":"21","author":"M Sadelain","year":"2009","unstructured":"Sadelain M, Brentjens R, Riviere I . The promise and potential pitfalls of chimeric antigen receptors. Curr Opin Immunol 2009; 21: 215\u2013223.","journal-title":"Curr Opin Immunol"},{"key":"BFleu2017145_CR8","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/nri1729","volume":"5","author":"MH Kershaw","year":"2005","unstructured":"Kershaw MH, Teng MWL, Smyth MJ, Darcy PK . Supernatural T cells: genetic modification of T cells for cancer therapy. Nat Rev Immunol 2005; 5: 928\u2013940.","journal-title":"Nat Rev Immunol"},{"key":"BFleu2017145_CR9","doi-asserted-by":"publisher","first-page":"4099","DOI":"10.1182\/blood-2010-04-281931","volume":"116","author":"JN Kochenderfer","year":"2010","unstructured":"Kochenderfer JN, Wilson WH, Janik JE, Dudley ME, Stetler-Stevenson M, Feldman SA et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize CD19. Blood 2010; 116: 4099\u20134102.","journal-title":"Blood"},{"key":"BFleu2017145_CR10","doi-asserted-by":"publisher","first-page":"1507","DOI":"10.1056\/NEJMoa1407222","volume":"371","author":"SL Maude","year":"2014","unstructured":"Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med 2014; 371: 1507\u20131517.","journal-title":"N Engl J Med"},{"key":"BFleu2017145_CR11","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1182\/blood-2014-12-615898","volume":"126","author":"DW Lee","year":"2015","unstructured":"Lee DW, Stetler-Stevenson M, Yuan CM, Yuan CM, Fry TJ, Shah NN et al. Safety and response of incorporating CD19 chimeric antigen receptor T cell therapy in typical salvage regimens for children and young adults with acute lymphoblastic leukemia. Blood 2015; 126: 684.","journal-title":"Blood"},{"key":"BFleu2017145_CR12","doi-asserted-by":"publisher","first-page":"224ra25","DOI":"10.1126\/scitranslmed.3008226","volume":"6","author":"ML Davila","year":"2014","unstructured":"Davila ML, Riviere I, Wang X, Bartido S, Park J, Curran K et al. Efficacy and toxicity management of 19-28z CAR-T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med 2014; 6: 224ra25.","journal-title":"Sci Transl Med"},{"key":"BFleu2017145_CR13","doi-asserted-by":"crossref","first-page":"3774","DOI":"10.1182\/blood.V126.23.3774.3774","volume":"126","author":"Dong Lujia","year":"2015","unstructured":"Lujia Dong, Lung-Ji Chang, Zhiyong Gao, Dao-Pei Lu, Jian-Ping Zhang, Jing-Bo Wang et al. Chimeric antigen receptor 4SCAR19-modified T cells in acute lymphoid leukemia: a phase II multi-center clinical trial in China. Blood 2015; 126: 3774.","journal-title":"Blood"},{"key":"BFleu2017145_CR14","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1182\/blood.V126.23.682.682","volume":"126","author":"JH Park","year":"2015","unstructured":"Park JH, Riviere I, Wang X, Bernal Y, Purdon T, Halton E et al. Implications of minimal residual disease negative complete remission (MRD-CR) and allogeneic stem cell transplant on safety and clinical outcome of CD19-targeted 19-28z CAR modified T cells in adult pts with relapsed, refractory B-cell ALL. Blood 2015; 126: 682.","journal-title":"Blood"},{"key":"BFleu2017145_CR15","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1182\/blood.V124.21.311.311","volume":"124","author":"P Kebriaei","year":"2014","unstructured":"Kebriaei P, Huls H, Singh H, Olivares S, Figliola M, Maiti S et al. Adoptive therapy using Sleeping Beauty gene transfer system and artificial antigen presenting cells to manufacture T cells expressing CD19-specific chimeric antigen receptor. Blood 2014; 124: 311.","journal-title":"Blood"},{"key":"BFleu2017145_CR16","doi-asserted-by":"publisher","first-page":"177ra38","DOI":"10.1126\/scitranslmed.3005930","volume":"5","author":"RJ Brentjens","year":"2013","unstructured":"Brentjens RJ, Davila ML, Riviere I, Park JH, Wang X, Cowell LG et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med 2013; 5: 177ra38.","journal-title":"Sci Transl Med"},{"issue":"15_suppl","key":"BFleu2017145_CR17","doi-asserted-by":"publisher","first-page":"7003","DOI":"10.1200\/JCO.2016.34.15_suppl.7003","volume":"34","author":"Jae Hong Park","year":"2016","unstructured":"Park JH, Riviere I, Wang X, Purdon T, Sadelain M, Brentjens RJ . Impact of disease burden on long-term outcome of 19-28z CAR modified T cells in adult patients with relapsed B-ALL. J Clin Oncol 2016; 34: (abstract 7003).","journal-title":"Journal of Clinical Oncology"},{"key":"BFleu2017145_CR18","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1172\/JCI85309","volume":"126","author":"CJ Turtle","year":"2016","unstructured":"Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M et al. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest 2016; 126: 2123\u20132138.","journal-title":"J Clin Invest"},{"issue":"15_suppl","key":"BFleu2017145_CR19","doi-asserted-by":"publisher","first-page":"7002","DOI":"10.1200\/JCO.2016.34.15_suppl.7002","volume":"34","author":"Noelle V. Frey","year":"2016","unstructured":"Frey NV, Shaw PA, Hexner EO, Gill S, Marcucci K, Luger SM et al. Optimizing chimeric antigen receptor (CAR)T cell therapy for adult patients with relapsed or refractory (R\/R) acute lymphoblastic leukemia (ALL). J Clin Oncol 2016; 34: (abstract 7002).","journal-title":"Journal of Clinical Oncology"},{"key":"BFleu2017145_CR20","first-page":"1","volume":"22","author":"J Pan","year":"2016","unstructured":"Pan J, Zhang Y, Zhao YL, Yang JF, Zhang JP, Liu HX et al. Impact of clinical factors on outcome of leukemia patients with TLS-ERG fusion gene. Leuk Lymphoma 2016; 22: 1\u20139.","journal-title":"Leuk Lymphoma"},{"key":"BFleu2017145_CR21","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1038\/nbt1227","volume":"24","author":"AH Chang","year":"2006","unstructured":"Chang AH, Stephan MT, Sadelain M . Stem cell\u2013derived erythroid cells mediate long-term systemic protein delivery. Nat Biotechnol 2006; 24: 1017\u20131021.","journal-title":"Nat Biotechnol"},{"key":"BFleu2017145_CR22","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1038\/nm1676","volume":"13","author":"MT Stephan","year":"2007","unstructured":"Stephan MT, Ponomarev V, Brentjens RJ, Chang AH, Dobrenkov KV, Heller G et al. T cell\u2013encoded CD80 and 4-1BBL induce auto- and transcostimulation, resulting in potent tumor rejection. Nat Med 2007; 13: 1440\u20131449.","journal-title":"Nat Med"},{"key":"BFleu2017145_CR23","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","volume":"124","author":"DW Lee","year":"2014","unstructured":"Lee DW, Gardner R, Porter DL, Louis CU, Ahmed N, Jensen M et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014; 124: 188\u2013195.","journal-title":"Blood"},{"key":"BFleu2017145_CR24","unstructured":"US Department of Health and Human Services. Common terminology criteria for adverse events. V4. 03 2010.[EB\/OL]. Available at: http:\/\/evs.nci.nih.gov\/ftp1\/CTCAE\/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf."},{"key":"BFleu2017145_CR25","unstructured":"Alvarnas JC, Brown PA, Advani A, Aoun P, Ballen KK, Barta SK et alNCCN Clinical Practice Guidelines in Oncology: Acute Lymphoblastic Leukemia, Verison 1, 2016. Available at: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/all.pdf."},{"key":"BFleu2017145_CR26","doi-asserted-by":"publisher","first-page":"95ra73","DOI":"10.1126\/scitranslmed.3002842","volume":"3","author":"M Kalos","year":"2011","unstructured":"Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med 2011; 3: 95ra73.","journal-title":"Sci Transl Med"},{"key":"BFleu2017145_CR27","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1182\/blood.V126.23.681.681","volume":"126","author":"SA Grupp","year":"2015","unstructured":"Grupp SA, Maude SL, Shaw PA, Aplenc R, Barrett DM, Callahan C et al. Durable remissions in children with relapsed\/refractory ALL treated with T cells engineered with a CD19-targeted chimeric antigen receptor (CTL019). Blood 2015; 126: 681.","journal-title":"Blood"},{"key":"BFleu2017145_CR28","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/j.bbmt.2016.09.002","volume":"23","author":"SS Kenderian","year":"2016","unstructured":"Kenderian SS, Porter DL, Gill S . Chimeric antigen receptor T cells and hematopoietic cell transplantation: how not to put the CART before the horse. Biol Blood Marrow Transplant 2016; 23: 235\u2013246.","journal-title":"Biol Blood Marrow Transplant"},{"key":"BFleu2017145_CR29","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1016\/S0140-6736(14)61403-3","volume":"385","author":"DW Lee","year":"2015","unstructured":"Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet 2015; 385: 517\u2013528.","journal-title":"Lancet"},{"key":"BFleu2017145_CR30","doi-asserted-by":"publisher","first-page":"355ra116","DOI":"10.1126\/scitranslmed.aaf8621","volume":"8","author":"CJ Turtle","year":"2016","unstructured":"Turtle CJ, Hanafi LA, Berger C, Hudecek M, Pender B, Robinson E et al. Immunotherapy of non-Hodgkin\u2019s lymphoma with a defined ratio of CD8+ and CD4+ CD19-specific chimeric antigen receptor\u2013modified T cells. Sci Transl Med 2016; 8: 355ra116.","journal-title":"Sci Transl Med"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/leu2017145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/leu2017145","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/leu.2017.145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"https:\/\/www.nature.com\/articles\/leu2017145.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T13:37:01Z","timestamp":1648733821000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/leu2017145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,15]]},"references-count":30,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["BFleu2017145"],"URL":"https:\/\/doi.org\/10.1038\/leu.2017.145","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.727605193.793532117","asserted-by":"object"}]},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,15]]},"assertion":[{"value":"23 January 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2017","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2017","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 May 2017","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"AHC is also a founding member of Shanghai YaKe Biotechnology Ltd., a biotechnology company focused on research and development of tumor cell immunotherapy. YZ and SL are also employees of Shanghai YaKe Biotechnoloy Ltd. The remaining authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}