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      CAR T-cell therapy for a relapsed/refractory acute B-cell lymphoblastic lymphoma patient in the context of Li-Fraumeni syndrome

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          Abstract

          Background

          Li-Fraumeni syndrome (LFS) is characterized as an autosomal dominant cancer predisposition disorder caused by germline TP53 gene mutations. Both primary and therapy-related hematopoietic malignancies with LFS are associated with dismal outcomes with standard therapies and even allogenic stem cell transplantation (SCT).

          Case presentation

          We reported a relapsed/refractory acute B-cell lymphoblastic lymphoma (B-LBL) patient in the context of LFS. He was identified to harbor a TP53 c.818G>A (p.R273H) germline mutation, and his family history was significant for rectal carcinoma in his father, an unknown cancer in his sister and acute lymphoblastic leukemia in his brother and one of his sons. The patient received murine monoclonal anti-CD19 and anti-CD22 chimeric antigen receptor (CAR) T-cell “cocktail” therapy and achieved complete remission with negative minimal residual disease (MRD), as assessed by morphology and multiparameter flow cytometry. Fifteen months after murine monoclonal CAR T-cell “cocktail” therapy, the patient’s B-LBL recurred. Fortunately, a round of fully human monoclonal anti-CD22 CAR T-cell therapy was still effective in this patient, and he achieved CR again and continued to be followed. Each time after infusion, the CAR T-cells underwent extremely rapid exponential expansion, which may be due to the disruption of TP53, a gene that can functionally control cell cycle arrest. Grade 4 and grade 1 cytokine release syndrome occurred after the first and second rounds of CAR T-cell therapy, respectively.

          Conclusions

          This case provides the first report of the use of CAR T-cell therapy in a hematologic malignancy patient with LFS. As traditional chemotherapy and allogenic SCT are not effective therapy strategies for patients with hematologic malignancies and LFS, CAR T-cell therapy may be an alternate choice.

          ChiCTR-OPN-16008526 and ChiCTR1900023922.

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          Most cited references13

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          Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells

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            Soft-tissue sarcomas, breast cancer, and other neoplasms. A familial syndrome?

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              Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies

              Relapse following chemeric antigen receptor (CAR) T-cell therapy can arise from progressive loss of the CAR T cells or from loss of the target antigen by tumor cells. Wang et al report that using a mix of CAR T cells targeting CD19 and CD22 reduces relapse with antigen-negative tumor cells. However, a lack of CAR T-cell persistence leads to increased relapse with antigen-positive cells.
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                Author and article information

                Journal
                J Immunother Cancer
                J Immunother Cancer
                jitc
                jitc
                Journal for Immunotherapy of Cancer
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2051-1426
                2020
                28 April 2020
                : 8
                : 1
                : e000364
                Affiliations
                [1]departmentDepartment of Hematology , Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology , Wuhan, China
                Author notes
                [Correspondence to ] Jianfeng Zhou; jfzhou@ 123456tjh.tjmu.edu.cn ; Yi Xiao; yixiao@ 123456tjh.tjmu.edu.cn
                Author information
                http://orcid.org/0000-0002-7786-1226
                Article
                jitc-2019-000364
                10.1136/jitc-2019-000364
                7213909
                32345625
                f9e4eaf0-49d3-489f-9b62-442f36d65768
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 25 March 2020
                Categories
                Case Report
                1506
                Custom metadata
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                haematology,immunotherapy
                haematology, immunotherapy

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