Zhang Xiaomin, Wang Lixin, Qiao Jingqiao, Wang Shuhong, Wang Lijun, Liu Lian, Qin Jiading, Chen Ziren, Huang Wenfa, Zheng Yuanyuan, Peng Huixin, Mei Junhui, Wang Hongxin, Yu Chuan, Li Yisheng, Yu Li
Department of Hematology and Oncology, Shenzhen University General Hospital, International Cancer Center, Hematology Institution, Haoshi Cell Therapy Institute of Shenzhen University, Shenzhen University Medical School, Shenzhen University, Shenzhen, China.
Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, China.
Front Immunol. 2025 Jul 21;16:1617589. doi: 10.3389/fimmu.2025.1617589. eCollection 2025.
T (8; 21) acute myeloid leukemia (AML) is a special type of acute leukemia, and exhibits a heterogeneous prognosis, with a long-term relapse rate of about 40%. Once t(8; 21) AML patients experience relapse, they have an extremely poor prognosis, with a 5-year overall survival rate of less than 15%. Therefore, it is crucial to develop effective strategies to improve the prognosis of relapsed/refractory (R/R) t(8; 21) AML. CD19 is a specific B-cell surface marker, but it is aberrantly expressed in 50-80 % of t(8; 21) AML patients. CAR-T cells targeting aberrant cell-surface antigens could induce the depletion of tumor cells without the destruction of hematopoiesis. Therefore, CD19 might be a promising target for CAR-T cell therapy in R/R t(8; 21) AML with aberrant CD19 expression. The present study is aimed to explore the efficacy and safety of CD19 CAR-T cell therapy in R/R t(8;21) AML with aberrant CD19 expression.
In the present study, 3 R/R t(8;21) AML patients with aberrant CD19 expression were enrolled. After lymphodepleting chemotherapy, 3 patients received autologous CAR-T cell infusion at a dose of 1.0 × 10^6 cells/kg, 2.0 × 10^6 cells/kg, and 2.0 × 10^6 cells/kg, respectively.
They all achieved CD19 negativity approximately half a month after CD19 CAR-T cell infusion. These indicate CD19 CAR-T cell therapy is effective in R/R t(8;21) AML with aberrant CD19 expression. However, patient 1 and patient 2 rapidly relapsed within 3 months after CD19 CAR-T cell therapy. Subsequently, patient 1 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). Fortunately, patient 1 achieved mCR 2 months after allo-HSCT.
Considering the short-term remission of CD19 CAR-T cell therapy in R/R t(8;21) AML, allo-HSCT might be performed as soon as possible to consolidate the efficacy of CAR-T cell therapy and reduce the risk of relapse.
T（8；21）急性髓系白血病（AML）是一种特殊类型的急性白血病，预后具有异质性，长期复发率约为40%。一旦T（8；21）AML患者复发，其预后极差，5年总生存率低于15%。因此，制定有效的策略以改善复发/难治性（R/R）T（8；21）AML的预后至关重要。CD19是一种特异性B细胞表面标志物，但在50%-80%的T（8；21）AML患者中异常表达。靶向异常细胞表面抗原的嵌合抗原受体T细胞（CAR-T）可诱导肿瘤细胞耗竭而不破坏造血功能。因此，对于CD19异常表达的R/R T（8；21）AML，CD19可能是CAR-T细胞治疗的一个有前景的靶点。本研究旨在探讨CD19 CAR-T细胞治疗在CD19异常表达的R/R T（8；21）AML中的疗效和安全性。
本研究纳入3例CD19异常表达的R/R T（8；21）AML患者。在进行淋巴细胞清除化疗后，3例患者分别接受了剂量为1.0×10^6细胞/kg、2.0×10^6细胞/kg和2.0×10^6细胞/kg的自体CAR-T细胞输注。
在CD19 CAR-T细胞输注后约半个月，他们均实现了CD19阴性。这些结果表明CD19 CAR-T细胞治疗对于CD19异常表达的R/R T（8；21）AML有效。然而，患者1和患者2在CD19 CAR-T细胞治疗后3个月内迅速复发。随后，患者1接受了异基因造血干细胞移植（allo-HSCT）。幸运的是，患者1在allo-HSCT后2个月达到了微小残留病完全缓解（mCR）。
考虑到CD19 CAR-T细胞治疗在R/R T（8；21）AML中的短期缓解情况，可能需要尽快进行allo-HSCT以巩固CAR-T细胞治疗的疗效并降低复发风险。
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