{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:25:57Z","timestamp":1790040357110,"version":"4.0.1"},"reference-count":38,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed\/refractory (r\/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r\/r B-ALL. We searched MEDLINE, Embase, and the Cochrane Library for prospective interventional studies and included published studies of \u22655 patients with median age at enrollment of \u226518 years. Risk of bias was assessed with a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean complete remission (CR) rate was 81% and the measurable residual disease (MRD)\u2013negative remission rate was 81% at 4 weeks after CAR-T infusion. With median follow-up across studies of 24 months, the cumulative 12-month probabilities of progression-free survival (PFS) and overall survival (OS) were 37% (95% CI, 26-48) and 57% (95% CI, 49-65), respectively. Relapse occurred in 40.3% of cases; target antigen was retained in 73.2% of relapses. Across studies, any grade of cytokine release syndrome (CRS) occurred in 82% of patients (95% CI, 61-95) and grade 3 or higher CRS in 27% (95% CI, 18-36). Neurotoxicity of any grade occurred in 34% of patients (95% CI, 24-47) and grade 3 or higher in 14% (95% CI, 1-25). In summary, CAR-T therapy achieves high early remission rates in adults with r\/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020003482","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T01:42:16Z","timestamp":1633484536000},"page":"1608-1618","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia"],"prefix":"10.1182","volume":"6","author":[{"given":"Punita","family":"Grover","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, University of Cincinnati Medical Center, Cincinnati, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Veilleux","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Health Research and Policy, Stanford University, Stanford, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-1561","authenticated-orcid":false,"given":"Ryan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Previtera","sequence":"additional","affiliation":[{"name":"Health Sciences Library, University of Cincinnati, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Curran","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Cincinnati Medical Center, Cincinnati, OH;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9887-6136","authenticated-orcid":false,"given":"Lori","family":"Muffly","sequence":"additional","affiliation":[{"name":"Division of Blood and Marrow Transplantation and Cellular Therapy, Stanford University, CA;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"issue":"4","key":"2022030716284002000_B1","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1365-2141.2012.09095.x","article-title":"Outcomes in older adults with acute lymphoblastic leukaemia (ALL): results from the international MRC UKALL XII\/ECOG2993 trial","volume":"157","author":"Sive","year":"2012","journal-title":"Br J Haematol."},{"issue":"4","key":"2022030716284002000_B2","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1200\/JCO.2016.69.0073","article-title":"High Frequency and Poor Outcome of Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia in Adults","volume":"35","author":"Roberts","year":"2017","journal-title":"J Clin Oncol."},{"issue":"5","key":"2022030716284002000_B3","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1056\/NEJMoa1709866","article-title":"Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia","volume":"378","author":"Maude","year":"2018","journal-title":"N Engl J Med."},{"issue":"21","key":"2022030716284002000_B4","doi-asserted-by":"crossref","first-page":"5414","DOI":"10.1182\/bloodadvances.2020003092","article-title":"Real-world evidence of tisagenlecleucel for pediatric acute lymphoblastic leukemia and non-Hodgkin lymphoma [published correction appears in Blood Adv. 2021;5(4):1136]","volume":"4","author":"Pasquini","year":"2020","journal-title":"Blood Adv."},{"issue":"4","key":"2022030716284002000_B5","doi-asserted-by":"crossref","first-page":"e334","DOI":"10.1016\/j.clml.2020.12.010","article-title":"Systematic review and meta-analysis of CD19-Specific CAR-T cell therapy in relapsed\/refractory acute lymphoblastic leukemia in the pediatric and young adult population: safety and efficacy outcomes","volume":"21","author":"Aamir","year":"2021","journal-title":"Clin Lymphoma Myeloma Leuk."},{"issue":"11","key":"2022030716284002000_B6","doi-asserted-by":"crossref","first-page":"e816","DOI":"10.1016\/S2352-3026(20)30277-5","article-title":"Anti-CD19 chimeric antigen receptor T-cell therapy in acute lymphocytic leukaemia: a systematic review and meta-analysis","volume":"7","author":"Anagnostou","year":"2020","journal-title":"Lancet Haematol."},{"key":"2022030716284002000_B7","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions.","author":"Higgins","year":"2019"},{"issue":"71","key":"2022030716284002000_B8","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ."},{"issue":"10299","key":"2022030716284002000_B9","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S0140-6736(21)01222-8","article-title":"KTE-X19 for relapsed or refractory adult B-cell acute lymphoblastic leukaemia: phase 2 results of the single-arm, open-label, multicentre ZUMA-3 study","volume":"398","author":"Shah","year":"2021","journal-title":"Lancet."},{"issue":"1","key":"2022030716284002000_B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/2046-4053-4-1","article-title":"Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement","volume":"4","author":"Moher","year":"2015","journal-title":"Syst Rev."},{"key":"2022030716284002000_B11","article-title":"A systematic review to study the outcomes and toxicities of chimeric antigen T cell therapy (CAR-T) in adults with B-acute lymphoblastic leukemia (B-ALL)","author":"Grover"},{"issue":"12","key":"2022030716284002000_B12","doi-asserted-by":"crossref","first-page":"e019321","DOI":"10.1136\/bmjopen-2017-019321","article-title":"Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis","volume":"7","author":"Grigor","year":"2017","journal-title":"BMJ Open."},{"issue":"3","key":"2022030716284002000_B13","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1002\/sim.8396","article-title":"Exact inference for the random-effect model for meta-analyses with rare events","volume":"39","author":"Gronsbell","year":"2020","journal-title":"Stat Med."},{"issue":"2","key":"2022030716284002000_B14","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1111\/biom.12998","article-title":"Exact inference on the random-effects model for meta-analyses with few studies","volume":"75","author":"Michael","year":"2019","journal-title":"Biometrics."},{"issue":"1","key":"2022030716284002000_B15","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13045-020-00856-8","article-title":"Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia [published correction appears in J Hematol Oncol. 2020;13(1):53]","volume":"13","author":"Dai","year":"2020","journal-title":"J Hematol Oncol."},{"issue":"11","key":"2022030716284002000_B16","doi-asserted-by":"crossref","first-page":"e1027469","DOI":"10.1080\/2162402X.2015.1027469","article-title":"Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia","volume":"4","author":"Dai","year":"2015","journal-title":"OncoImmunology."},{"issue":"5","key":"2022030716284002000_B17","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1200\/JCO.19.01892","article-title":"Optimizing Chimeric Antigen Receptor T-Cell Therapy for Adults With Acute Lymphoblastic Leukemia","volume":"38","author":"Frey","year":"2020","journal-title":"J Clin Oncol."},{"issue":"1","key":"2022030716284002000_B18","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13045-020-00953-8","article-title":"Efficacy and safety of CD19 CAR T constructed with a new anti-CD19 chimeric antigen receptor in relapsed or refractory acute lymphoblastic leukemia","volume":"13","author":"Gu","year":"2020","journal-title":"J Hematol Oncol."},{"issue":"15","key":"2022030716284002000_B19","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1182\/blood-2018-11-883710","article-title":"Factors associated with durable EFS in adult B-cell ALL patients achieving MRD-negative CR after CD19 CAR T-cell therapy","volume":"133","author":"Hay","year":"2019","journal-title":"Blood."},{"issue":"9","key":"2022030716284002000_B20","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.clml.2020.04.007","article-title":"Allogeneic donor-derived anti-CD19 CAR T cell is a promising therapy for relapsed\/refractory B-ALL after allogeneic hematopoietic stem-cell transplantation","volume":"20","author":"Hua","year":"2020","journal-title":"Clin Lymphoma Myeloma Leuk."},{"issue":"13","key":"2022030716284002000_B21","doi-asserted-by":"crossref","first-page":"3297","DOI":"10.1158\/1078-0432.CCR-16-1799","article-title":"Potent anti-leukemia activities of chimeric antigen receptor-modified T cells against CD19 in chinese patients with relapsed\/refractory acute lymphocytic leukemia","volume":"23","author":"Hu","year":"2017","journal-title":"Clin Cancer Res."},{"issue":"10","key":"2022030716284002000_B22","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1002\/ajh.25582","article-title":"Anti-CD19 chimeric antigen receptor-modified T-cell therapy bridging to allogeneic hematopoietic stem cell transplantation for relapsed\/refractory B-cell acute lymphoblastic leukemia: An open-label pragmatic clinical trial","volume":"94","author":"Jiang","year":"2019","journal-title":"Am J Hematol."},{"issue":"3","key":"2022030716284002000_B23","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/bjh.15195","article-title":"Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB","volume":"181","author":"Li","year":"2018","journal-title":"Br J Haematol."},{"issue":"4","key":"2022030716284002000_B24","first-page":"20","article-title":"A phase I study of CAR-T bridging HSCT in patients with acute CD19+ relapse\/refractory B-cell leukemia","volume":"20","author":"Ma","year":"2020","journal-title":"Oncol Lett."},{"issue":"2","key":"2022030716284002000_B25","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1016\/j.ymthe.2020.09.027","article-title":"CART19-BE-01: A multicenter trial of ARI-0001 cell therapy in patients with CD19+ relapsed\/refractory malignancies","volume":"29","author":"Ort\u00edz-Maldonado","year":"2021","journal-title":"Mol Ther."},{"issue":"5","key":"2022030716284002000_B26","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1056\/NEJMoa1709919","article-title":"Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia","volume":"378","author":"Park","year":"2018","journal-title":"N Engl J Med."},{"issue":"2","key":"2022030716284002000_B27","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/bjh.16623","article-title":"Efficacy and safety of humanized anti-CD19-CAR-T therapy following intensive lymphodepleting chemotherapy for refractory\/relapsed B acute lymphoblastic leukaemia","volume":"191","author":"Wang","year":"2020","journal-title":"Br J Haematol."},{"issue":"1","key":"2022030716284002000_B28","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1182\/blood.2019000017","article-title":"Efficacy and safety of CAR19\/22 T-cell cocktail therapy in patients with refractory\/relapsed B-cell malignancies","volume":"135","author":"Wang","year":"2020","journal-title":"Blood."},{"issue":"6","key":"2022030716284002000_B29","doi-asserted-by":"crossref","first-page":"1563","DOI":"10.1038\/s41375-020-01056-6","article-title":"Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant","volume":"35","author":"Zhang","year":"2021","journal-title":"Leukemia."},{"issue":"2","key":"2022030716284002000_B30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current concepts in the diagnosis and management of cytokine release syndrome [published correction appears in Blood. 2015;126(8):1048]","volume":"124","author":"Lee","year":"2014","journal-title":"Blood."},{"issue":"4","key":"2022030716284002000_B31","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.bbmt.2018.12.758","article-title":"ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells","volume":"25","author":"Lee","year":"2019","journal-title":"Biol Blood Marrow Transplant."},{"key":"2022030716284002000_B32","author":"National Cancer Institute, Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program"},{"issue":"1","key":"2022030716284002000_B33","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13045-018-0571-y","article-title":"Grading of cytokine release syndrome associated with the CAR T cell therapy tisagenlecleucel [published correction appears in J Hematol Oncol. 2018;11(1):81]","volume":"11","author":"Porter","year":"2018","journal-title":"J Hematol Oncol."},{"issue":"12","key":"2022030716284002000_B34","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.3324\/haematol.2016.144311","article-title":"International reference analysis of outcomes in adults with B-precursor Ph-negative relapsed\/refractory acute lymphoblastic leukemia","volume":"101","author":"G\u00f6kbuget","year":"2016","journal-title":"Haematologica."},{"issue":"4","key":"2022030716284002000_B35","doi-asserted-by":"crossref","first-page":"589","DOI":"10.3324\/haematol.2009.014274","article-title":"Outcome after relapse of acute lymphoblastic leukemia in adult patients included in four consecutive risk-adapted trials by the PETHEMA Study Group","volume":"95","author":"Oriol","year":"2010","journal-title":"Haematologica."},{"issue":"8","key":"2022030716284002000_B36","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1056\/NEJMoa1509277","article-title":"Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia","volume":"375","author":"Kantarjian","year":"2016","journal-title":"N Engl J Med."},{"issue":"9","key":"2022030716284002000_B37","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1056\/NEJMoa1609783","article-title":"Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia","volume":"376","author":"Kantarjian","year":"2017","journal-title":"N Engl J Med."},{"key":"2022030716284002000_B38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1182\/blood-2020-134472","article-title":"Disease burden impacts outcomes in pediatric and young adult B-Cell acute lymphoblastic leukemia after commercial tisagenlecleucel: results from the Pediatric Real World CAR Consortium (PRWCC) [abstract]","volume":"136","author":"Schultz","year":"2020","journal-title":"Blood."}],"container-title":["Blood Advances"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/6\/5\/1608\/1877781\/advancesadv2020003482c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article-pdf\/6\/5\/1608\/1877781\/advancesadv2020003482c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T16:29:18Z","timestamp":1646670558000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/bloodadvances\/article\/6\/5\/1608\/477169\/Chimeric-antigen-receptor-T-cell-therapy-in-adults"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":38,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,3,8]]}},"URL":"https:\/\/doi.org\/10.1182\/bloodadvances.2020003482","relation":{},"ISSN":["2473-9529","2473-9537"],"issn-type":[{"value":"2473-9529","type":"print"},{"value":"2473-9537","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]}}}