{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T19:46:33Z","timestamp":1788637593765,"version":"build-2803163510"},"reference-count":139,"publisher":"SAABRON PRESS","issue":"1","license":[{"start":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T00:00:00Z","timestamp":1710288000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>CD19-directed Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of patients with B-cell acute lymphoblastic leukemia (B-ALL). Somewhat uniquely among oncologic clinical trials, early clinical development occurred simultaneously in both children and adults. In subsequent years however, the larger number of adult patients with relapsed\/refractory (r\/r) malignancies has led to accelerated development of multiple CAR T-cell products that target a variety of malignancies, resulting in six currently FDA-approved for adult patients. By comparison, only a single CAR-T cell therapy is approved by the FDA for pediatric patients: tisagenlecleucel, which is approved for patients \u2264 25 years with refractory B-cell precursor ALL, or B-cell ALL in second or later relapse. Tisagenlecleucel is also under evaluation in pediatric patients with relapsed\/refractory B-cell non-Hodgkin lymphoma, but is not yet been approved for this indication. All the other FDA-approved CD19-directed CAR-T cell therapies available for adult patients (axicabtagene ciloleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel) are currently under investigations among children, with preliminary results available in some cases. As the volume and complexity of data continue to grow, so too does the necessity of rapid assimilation and implementation of those data. This is particularly true when considering \u201catypical\u201d situations, e.g.\u00a0those arising when patients do not precisely conform to the profile of those included in pivotal clinical trials, or when alternative treatment options (e.g.\u00a0hematopoietic stem cell transplantation (HSCT) or bispecific T-cell engagers (BITEs)) are also available. We have therefore developed a relevant summary of the currently available literature pertaining to the use of CD19-directed CAR-T cell therapies in pediatric patients, and sought to provide guidance for clinicians seeking additional data about specific clinical situations.<\/jats:p>","DOI":"10.46989\/001c.94386","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T14:14:10Z","timestamp":1710339250000},"source":"Crossref","is-referenced-by-count":7,"title":["The Implementation of Chimeric Antigen Receptor (CAR) T-cell Therapy in Pediatric Patients: Where Did We Come From, Where Are We Now, and Where are We Going?"],"prefix":"10.46989","volume":"6","author":[{"given":"Tristan","family":"Knight E","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01njes783","id-type":"ROR","asserted-by":"publisher"}],"name":"Seattle Children's Hospital","department":["Cancer and Blood Disorders Center"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olalekan","family":"Oluwole","sequence":"additional","affiliation":[{"name":"Medicine Hematology and Oncology, Vanderbilt University Medical Center"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Kitko","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05dq2gs74","id-type":"ROR","asserted-by":"publisher"}],"name":"Vanderbilt University Medical Center","department":["Pediatrics"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"26435","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"issue":"24","key":"ref1","doi-asserted-by":"publisher","first-page":"6175","DOI":"10.1158\/1078-0432.ccr-18-0758","article-title":"Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia","volume":"24","author":"Karen Thudium Mueller","year":"2018","journal-title":"Clin Cancer Res","ISSN":"https:\/\/id.crossref.org\/issn\/1078-0432","issn-type":"print"},{"issue":"15_suppl","key":"ref2","doi-asserted-by":"publisher","first-page":"e15056","DOI":"10.1200\/jco.2018.36.15_suppl.e15056","article-title":"Considerations for tisagenlecleucel dosing rationale.","volume":"36","author":"Rakesh Awasthi","year":"2018","journal-title":"Journal of Clinical Oncology","ISSN":"https:\/\/id.crossref.org\/issn\/0732-183X","issn-type":"print"},{"issue":"12","key":"ref3","doi-asserted-by":"publisher","first-page":"3383","DOI":"10.1038\/s41375-021-01281-7","article-title":"Determinants of CD19-positive vs CD19-negative relapse after tisagenlecleucel for B-cell acute lymphoblastic leukemia","volume":"35","author":"Marie-Emilie Dourthe","year":"2021","journal-title":"Leukemia","ISSN":"https:\/\/id.crossref.org\/issn\/0887-6924","issn-type":"print"},{"issue":"1","key":"ref4","doi-asserted-by":"publisher","first-page":"12320","DOI":"10.1038\/ncomms12320","article-title":"CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity","volume":"7","author":"Elad Jacoby","year":"2016","journal-title":"Nature Communications","ISSN":"https:\/\/id.crossref.org\/issn\/2041-1723","issn-type":"print"},{"issue":"12","key":"ref5","doi-asserted-by":"publisher","first-page":"3382","DOI":"10.1038\/s41375-020-0831-z","article-title":"Frequent occurrence of CD19-negative relapse after CD19 CAR T and consolidation therapy in 14 TP53-mutated r\/r B-ALL children","volume":"34","author":"Jing Pan","year":"2020","journal-title":"Leukemia","ISSN":"https:\/\/id.crossref.org\/issn\/0887-6924","issn-type":"print"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"784024","DOI":"10.3389\/fped.2021.784024","article-title":"Chimeric Antigen Receptor T-Cell Therapy in Paediatric B-Cell Precursor Acute Lymphoblastic Leukaemia: Curative Treatment Option or Bridge to Transplant?","volume":"9","author":"Jochen Buechner","year":"2022","journal-title":"Frontiers in Pediatrics","ISSN":"https:\/\/id.crossref.org\/issn\/2296-2360","issn-type":"print"},{"issue":"1","key":"ref7","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1158\/2643-3230.bcd-21-0095","article-title":"Next-Generation Sequencing of Minimal Residual Disease for Predicting Relapse after Tisagenlecleucel in Children and Young Adults with Acute Lymphoblastic Leukemia","volume":"3","author":"Michael A. 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