Department of Pediatrics, Peking University People's Hospital, Beijing, China.
Research Department, Immunotech Applied Science Ltd, Beijing, China.
Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):e410-e414. doi: 10.1016/j.clml.2020.12.009. Epub 2020 Dec 16.
chimeric antigen receptor-modified T cell (CAR-T) therapy is an effective and promising treatment for refractory and multiply relapsed B-cell acute lymphoblastic leukemia (B-ALL). Because of its side effects and poor responses such as neurotoxicity and cytokine release syndrome, patients with central nervous system leukemia were excluded in most previous clinical trials of CAR-T treatment.
We enrolled 3 B-ALL patients with central nervous system leukemia relapse. They were infused with CD19-specific CAR-Ts, and their clinical responses were evaluated by bone marrow smear, flow cytometry, and cytogenetic alterations detected by quantitative PCR, interleukin-6, and the expansion and persistence of circulating CAR-Ts in peripheral blood and cerebrospinal fluid.
After CAR-T infusion, 2 of the 3 patients experienced bone marrow minimal residual disease-negative complete remission, and all patients tested negative for residual leukemia cells in cerebrospinal fluid tested by flow cytometry. These 3 patients experienced grade 2 or 3 cytokine release syndrome, which resolved completely after symptomatic treatment. None experienced neurotoxicity or needed further intensive care.
CAR-T infusion is a potentially effective treatment for relapsed/refractory B-ALL patients with central nervous system involvement.
嵌合抗原受体修饰的 T 细胞（CAR-T）疗法是一种治疗难治性和复发性 B 细胞急性淋巴细胞白血病（B-ALL）的有效且有前途的方法。由于其副作用和不良反应，如神经毒性和细胞因子释放综合征，大多数之前的 CAR-T 治疗临床试验都排除了中枢神经系统白血病患者。
我们纳入了 3 例中枢神经系统白血病复发的 B-ALL 患者。他们输注了 CD19 特异性 CAR-T，并通过骨髓涂片、流式细胞术以及通过定量 PCR 检测的细胞遗传学改变、白细胞介素-6 以及外周血和脑脊液中循环 CAR-T 的扩增和持续情况评估其临床反应。
CAR-T 输注后，3 例患者中有 2 例骨髓微小残留病灶阴性完全缓解，所有患者的流式细胞术检测脑脊液中残留白血病细胞均为阴性。这 3 例患者发生 2 级或 3 级细胞因子释放综合征，经对症治疗后完全缓解。无患者发生神经毒性或需要进一步重症监护。
CAR-T 输注是治疗伴有中枢神经系统受累的复发/难治性 B-ALL 患者的一种潜在有效方法。
