{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:21:59Z","timestamp":1790842919158,"version":"4.1.0"},"reference-count":13,"publisher":"American Society of Hematology","issue":"4","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Remarkable complete response rates have been shown with tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy targeting CD19, in patients up to age 26 years with refractory\/relapsed B-cell acute lymphoblastic leukemia; it is US Food and Drug Administration approved for\u00a0this indication. Currently, patients receive a single dose of tisagenlecleucel across a wide dose\u00a0range of 0.2 to 5.0\u00a0\u00d7 106 and 0.1 to 2.5\u00a0\u00d7 108 CAR T cells per kg for patients \u226450 and &amp;gt;50 kg, respectively. The effect of cell dose on survival and remission is not yet well established. Our primary goal was to determine if CAR T-cell dose affects overall survival (OS), event-free survival (EFS), or relapse-free-survival (RFS) in tisagenlecleucel recipients. Retrospective data were collected from Pediatric Real World CAR Consortium member institutions and included 185 patients infused with commercial tisagenlecleucel. The median dose of viable transduced CAR T cells was 1.7\u00a0\u00d7 106 CAR T cells per kg. To assess the impact of cell dose, we divided responders into dose quartiles: 0.134 to 1.300\u00a0\u00d7 106 (n\u00a0= 48 [27%]), 1.301 to 1.700\u00a0\u00d7 106 (n\u00a0= 46 [26%]), 1.701 to 2.400\u00a0\u00d7\u00a0106 (n\u00a0= 43 [24%]), and 2.401 to 5.100\u00a0\u00d7 106 (n\u00a0= 43 [24%]). OS, EFS, and RFS were improved in patients who received higher doses of tisagenlecleucel (P\u00a0= .031, .0079, and .0045, respectively). Higher doses of tisagenlecleucel were not associated with increased toxicity. Because the current tisagenlecleucel package insert dose range remains broad, this work has implications in regard to\u00a0targeting higher cell doses, within the approved dose range, to optimize patients\u2019 potential for long-standing remission.<\/jats:p>","DOI":"10.1182\/bloodadvances.2022007246","type":"journal-article","created":{"date-parts":[[2022,8,8]],"date-time":"2022-08-08T13:03:40Z","timestamp":1659963820000},"page":"541-548","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":48,"title":["Higher doses of tisagenlecleucel are associated with improved outcomes: a report from the pediatric real-world CAR consortium"],"prefix":"10.1182","volume":"7","author":[{"given":"Heather E.","family":"Stefanski","sequence":"first","affiliation":[{"name":"1Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5900-9745","authenticated-orcid":false,"given":"Anne","family":"Eaton","sequence":"additional","affiliation":[{"name":"2Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Baggott","sequence":"additional","affiliation":[{"name":"3Division of Hematology\/Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0471-9883","authenticated-orcid":false,"given":"Jenna","family":"Rossoff","sequence":"additional","affiliation":[{"name":"4Division of Pediatric Hematology, Oncology and Stem Cell Transplantation, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7097-5917","authenticated-orcid":false,"given":"Michael R.","family":"Verneris","sequence":"additional","affiliation":[{"name":"5Center for Cancer and Blood Disorders, Children\u2019s Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8589-3087","authenticated-orcid":false,"given":"Snehit","family":"Prabhu","sequence":"additional","affiliation":[{"name":"6Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly L.","family":"Pacenta","sequence":"additional","affiliation":[{"name":"7Department of Pediatrics, University of Texas Southwestern Medical Center\/Children\u2019s Health, Dallas, TX"},{"name":"8Division of Hematology and Oncology, Cook Children\u2019s Medical Center, Fort Worth, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine L.","family":"Phillips","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, University of Cincinnati, Cincinnati, OH"},{"name":"10Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie-An","family":"Talano","sequence":"additional","affiliation":[{"name":"11Division of Hematology\/Oncology\/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Moskop","sequence":"additional","affiliation":[{"name":"11Division of Hematology\/Oncology\/Blood and Marrow Transplantation, Department of Pediatrics, Medical College of Wisconsin and Children\u2019s Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven P.","family":"Margossian","sequence":"additional","affiliation":[{"name":"12Pediatric Hematology-Oncology, Dana-Farber\/Boston Children\u2019s Cancer and Blood Disorders Center, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary Douglas","family":"Myers","sequence":"additional","affiliation":[{"name":"13Division of Hematology and Oncology, Children\u2019s Mercy Hospital, University of Missouri Kansas City, Kansas City, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole A.","family":"Karras","sequence":"additional","affiliation":[{"name":"14Department of Pediatrics, City of Hope National Medical Center, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8653-1069","authenticated-orcid":false,"given":"Patrick A.","family":"Brown","sequence":"additional","affiliation":[{"name":"15Department of Oncology, Sidney Kimmel Cancer Center, John Hopkins School of Medicine, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7689-343X","authenticated-orcid":false,"given":"Muna","family":"Qayed","sequence":"additional","affiliation":[{"name":"16Winship Cancer Institute, Emory University and Children\u2019s Healthcare of Atlanta, Atlanta, GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Hermiston","sequence":"additional","affiliation":[{"name":"17Pediatric Hematology\/Oncology, Department of Pediatrics, Benioff Children\u2019s Hospital, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash","family":"Satwani","sequence":"additional","affiliation":[{"name":"18Division of Pediatric Hematology, Oncology and Stem Cell Transplant, Department of Pediatrics, Columbia University Irving Medical Center, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Christa","family":"Krupski","sequence":"additional","affiliation":[{"name":"9Department of Pediatrics, University of Cincinnati, Cincinnati, OH"},{"name":"10Cancer and Blood Disease Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy K.","family":"Keating","sequence":"additional","affiliation":[{"name":"5Center for Cancer and Blood Disorders, Children\u2019s Hospital of Colorado, University of Colorado School of Medicine, Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Wilcox","sequence":"additional","affiliation":[{"name":"13Division of Hematology and Oncology, Children\u2019s Mercy Hospital, University of Missouri Kansas City, Kansas City, MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cara A.","family":"Rabik","sequence":"additional","affiliation":[{"name":"19Division of Hematologic Malignancies I, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8405-1141","authenticated-orcid":false,"given":"Vanessa A.","family":"Fabrizio","sequence":"additional","affiliation":[{"name":"20Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"21Department of Pediatrics, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasant","family":"Chinnabhandar","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Yasemin","family":"Goksenin","sequence":"additional","affiliation":[{"name":"17Pediatric Hematology\/Oncology, Department of Pediatrics, Benioff Children\u2019s Hospital, University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Curran","sequence":"additional","affiliation":[{"name":"20Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY"},{"name":"21Department of Pediatrics, Weill Cornell Medical College, New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0359-9023","authenticated-orcid":false,"given":"Crystal L.","family":"Mackall","sequence":"additional","affiliation":[{"name":"6Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA"},{"name":"22Division of Hematology and Oncology, Department of Pediatrics, Stanford University School of Medicine, Stanford, 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