Htun Kyaw Thu, Gong Qiang, Ma Le, Wang Ping, Tan Ya, Wu Guangsheng, Chen Jieping
Department of Hematology, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China.
Hematology Department, First Affiliated Hospital of Shihezi University, Shihezi, China.
Front Oncol. 2021 Aug 26;11:699946. doi: 10.3389/fonc.2021.699946. eCollection 2021.
In recent decades, survival was significantly improved in B cell acute lymphoblastic leukemia (B-ALL) patients. But refractory and relapsed B-ALL still has aggressive clinical behavior and poor prognosis. Especially, the patients with central nervous system infiltration is very difficult to achieve complete remissions with routine treatment. Chimeric antigen receptor-modified T-cell therapy targeting CD-19 has shown to be a beneficial treatment approach in refractory and relapsed B cell acute lymphoblastic leukemia (r/r ALL). However, there are very few studies reporting to treatment of refractory and relapsed B cell ALL with central nervous system infiltration. Here, we reported one single case of a patient diagnosed with relapsed B cell ALL with CNS infiltration who was successfully treated by second generation CAR containing a co-stimulator CD28 or 4-1BB therapy. Long-term proliferation of CAR-T cells in peripheral blood and bone marrow was observed more than 18 months. After CAR-T treatment, the patient got toxicity of grade 1 cytokine release syndrome and achieved significantly 36 months event free survival of follow-up. It is suggested that CD-19 CAR containing CD28 or 4-1BB costimulatory may be an effective therapy in refractory and relapsed B cell ALL with central nervous system infiltration. Its toxicity is mild, and its safety is high. ClinicalTrials.gov Identifier: NCT02349698.
近几十年来，B细胞急性淋巴细胞白血病（B-ALL）患者的生存率有了显著提高。但难治性和复发性B-ALL仍具有侵袭性临床行为且预后较差。特别是，中枢神经系统浸润的患者采用常规治疗很难实现完全缓解。靶向CD-19的嵌合抗原受体修饰T细胞疗法已被证明是难治性和复发性B细胞急性淋巴细胞白血病（r/r ALL）的一种有效治疗方法。然而，很少有研究报道治疗伴有中枢神经系统浸润的难治性和复发性B细胞ALL。在此，我们报告了一例诊断为伴有中枢神经系统浸润的复发性B细胞ALL患者，该患者通过含共刺激分子CD28或4-1BB的第二代CAR疗法成功治愈。观察到CAR-T细胞在外周血和骨髓中持续增殖超过18个月。CAR-T治疗后，患者出现1级细胞因子释放综合征毒性反应，并在随访中显著实现了36个月的无事件生存期。提示含CD28或4-1BB共刺激分子的CD-19 CAR可能是治疗伴有中枢神经系统浸润的难治性和复发性B细胞ALL的有效疗法。其毒性轻微，安全性高。ClinicalTrials.gov标识符：NCT02349698。
