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KMID : 0939920220540030917
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대한암학회지
2022 Volume.54 No. 3 p.917 ~ p.925
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Outcomes of Anti-CD19 CAR-T Treatment of Pediatric B-ALL with Bone Marrow and Extramedullary Relapse
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Wan Xinyu
Yang Xiaomin
Yang Fan
Wang Tianyi
Ding Lixia
Song Lili
Miao Yan
Tang Yanjing
Lu Jun
Li Benshang
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Abstract
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Purpose: Anti-CD19 chimeric antigen receptor T-cell (19CAR-T) immunotherapy has achieved impressive clinical results in 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.
Materials and Methods: CAR-T cells were generated by transfection of primary human T lymphocytes with a lentiviral vector expressing anti-CD19 single-chain antibody fragments with the cytoplasmic domains of 4-1BB and CD3ζ, and used to infuse patients diagnosed as having r/r B-ALL with extramedullary origination. Clinical responses were evaluated by the use of bone marrow aspiration, imaging, and flow cytometry.
Results: Eight patients received 19CAR-T infusion and all attained complete remission (CR). Only one patient was bridged to hematopoietic stem cell transplantation (HSCT). Although three patients relapsed after infusion, they received 19/22CAR-T infusion sequentially and attained a second remission. To date, five patients are in continuous CR and all eight patients are still alive. The mean follow-up time was 21.9 months, while the 24-month estimated event-free survival is 51.4%.
Conclusion: 19CAR-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, a second CAR-T therapy creates another opportunity for remission for subsequent HSCT.
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KEYWORD
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B-ALL, Extramedullary relapse, CD19 CAR-T, Second CAR-T
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