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      Sequential CD19/22 CAR T-cell immunotherapy following autologous stem cell transplantation for central nervous system lymphoma

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          Abstract

          Chimeric antigen receptor (CAR) T-cell immunotherapy following autologous stem cell transplantation (ASCT) is a promising method for refractory or relapsed multiple myeloma, but explicit data for central nervous system lymphoma (CNSL) are lacking. Here, we treated 13 CNSL patients with ASCT sequential CD19/22 CAR T-cell infusion and simultaneously evaluated the clinical efficacy and toxicity. The 13 CNSL patients analyzed included four primary CNSL and nine secondary CNSL patients. Patients 1 and 10, who had complete remission status before enrollment, maintained clinical efficacy without recurrence. Nine of the remaining 11 patients responded to our protocol with a median durable time of 14.03 months, and the overall response and complete remission rate were 81.81% and 54.55%, respectively. No patient suffered grades 3–4 cytokine-release syndrome (CRS), and only patient 10 experienced severe immune effector cell-associated neurotoxicity syndrome (ICANS). In addition, increases in serum ferritin and interleukin-6 levels were often accompanied by CRS and ICANS. After a median follow-up time of 14.20 months, the estimated 1-year progression-free survival and overall survival rates were 74.59% and 82.50%, respectively. Sequential CD19/22 CAR T-cell immunotherapy following ASCT as a novel method for CNSL appears to have encouraging long-term efficacy with relatively manageable side effects.

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          Most cited references47

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          Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma

          In a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.
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            Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia

            In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
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              Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma

              Patients with diffuse large B-cell lymphoma that is refractory to primary and second-line therapies or that has relapsed after stem-cell transplantation have a poor prognosis. The chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel targets and eliminates CD19-expressing B cells and showed efficacy against B-cell lymphomas in a single-center, phase 2a study.
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                Author and article information

                Contributors
                jfzhou@tjh.tjmu.edu.cn
                yixiao@tjh.tjmu.edu.cn
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                15 July 2021
                15 July 2021
                July 2021
                : 11
                : 7
                : 131
                Affiliations
                GRID grid.33199.31, ISNI 0000 0004 0368 7223, Department of Hematology, Tongji Hospital, Tongji Medical College, , Huazhong University of Science and Technology, ; Wuhan, Hubei China
                Author information
                http://orcid.org/0000-0002-8708-9743
                http://orcid.org/0000-0002-2782-0311
                http://orcid.org/0000-0002-1332-9230
                http://orcid.org/0000-0001-7274-6774
                Article
                523
                10.1038/s41408-021-00523-2
                8282870
                34267187
                ee5c0633-30a8-4c78-a0a4-a3425e6fbd74
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 28 April 2021
                : 27 June 2021
                : 5 July 2021
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001809, National Natural Science Foundation of China (National Science Foundation of China);
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award ID: 81873444, 82070213
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                cancer immunotherapy,lymphoma
                Oncology & Radiotherapy
                cancer immunotherapy, lymphoma

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