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Treatment Outcome of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse by Anti-CD19 CAR-T
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  • Xinyu Wan,
  • Fan Yang,
  • Xiaomin Yang,
  • tianyi Wang,
  • Lixia Ding,
  • Yan Miao,
  • Xiang Wang,
  • Yani Ma,
  • Chengjuan Luo,
  • Jingyan Tang,
  • Longjun Gu,
  • Jing Chen,
  • Yanjing Tang,
  • Jun Lu,
  • Benshang Li
Xinyu Wan
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Fan Yang
Department of Hematology/Oncology, Children's Hospital of Soochow University
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Xiaomin Yang
Shanghai Children’s Medical Center, Shanghai Jiao Tong University, School of Medicine
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tianyi Wang
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Lixia Ding
Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine
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Yan Miao
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Xiang Wang
Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine
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Yani Ma
Shanghai Children’s Medical Center, Shanghai Jiaotong University School of Medicine
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Chengjuan Luo
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Jingyan Tang
Shanghai children's medical center
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Longjun Gu
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Jing Chen
Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine
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Yanjing Tang
Shanghai Children’s Medical Center, Shanghai Jiao Tong University, School of Medicine
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Jun Lu
Children’s Hospital of Soochow University
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Benshang Li
Shanghai Childrens Medical Center Affiliated to Shanghai Jiaotong University School of Medicine
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Abstract

Background: Anti-CD19 Chimeric Antigen Receptor T-Cell Immunotherapy (19CAR-T) has achieved impressive clinical achievements in both adult and pediatric relapsed/refractory (r/r) B-lineage acute lymphoblastic leukemia (B-ALL). However, the application and effect of CAR-T therapy in B-ALL patients with extramedullary relapse are rarely issued even disqualified in some clinical trials. Here, we examined the efficacy of 19CAR-T in patients with both bone marrow and extramedullary involvement. Methods: CAR-T cells were generated by a lentiviral vector transfection into primary human T lymphocytes to express anti-CD19 and anti-CD22 single chain antibody fragments (scFvs) with the cytoplasmic domains of 4-1BB and CD3ζ. Patients diagnosed as r/r B-ALL with extramedullary origination were infused with anti-CD19 CAR-T cells. The clinical responses were evaluated by bone marrow aspiration, imaging, and flow cytometry examination. Results: A total of 8 patients received 19CAR-T infusion and all of them acquired complete remission (CR), in which only 1 patient was bridged to hematopoietic stem cell transplantation (HSCT). Even though there were 3 patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and acquired the second remission. To date, 5 patients are continuous CR, and all patients are still alive. The mean follow-up time was 21.9 months while the 24-month estimated event-free survival (EFS) is 51.4%. Conclusions: Anti-CD19 CAR-T therapy can lead to clinical remission for extramedullary relapsed pediatric B-ALL patients. However, the problem of CD19+ relapses after CAR-T remained to be solved. For patients relapsing after CAR-T, the second CAR-T therapy suggests creating another opportunity of remission for subsequent HSCT.