肿瘤细胞治疗研究
英文原题：The Autologous Hematopoietic Stem Cells Transplantation Combination-Based Chimeric Antigen Receptor T-Cell Therapy Improves Outcomes of Relapsed/Refractory Central Nervous System B-Cell Lymphoma.
CAR T细胞疗法可增强其治疗晚期复发/难治性CNS B细胞淋巴瘤的疗效，而ASCT联合CART可诱导持久缓解和OS，且副作用可控。
目的：探讨CAR T细胞疗法在晚期复发/难治性中枢神经系统B细胞淋巴瘤中的有效性和安全性，并比较自体干细胞移植（ASCT）联合CAR T细胞疗法与序贯CART疗法对患者生存的影响。
该回顾性分析基于17例晚期复发/难治性中枢神经系统B细胞淋巴瘤患者的数据。在CAR T细胞输注前应用桥接化疗以进一步降低肿瘤负荷。对于自体造血干细胞成功采集的患者，采用含thiotepa的预处理方案进行ASCT后CD19/20/22CAR T细胞免疫治疗，同时应用序贯CD19/CD20/CD22CAR T细胞治疗。对于淋巴细胞清除，患者在CAR T细胞输注前接受bendamustine或fludarabine单药治疗或fludarabine联合cyclophosphamide治疗。
在17例患者中，8例完成了ASCT联合CART细胞治疗，9例完成了单纯CART细胞治疗。输注后3个月疗效评估中，客观缓解率（ORR）为12/17（71%），完全缓解率（CRR）为11/17（65%）。ASCT组和非ASCT组的CRR分别为100%和44.4%（P < 0.01）。中位无进展生存期为16.3（2.6-24.5）个月，中位总生存期为19.3（6-24.5）个月。接受ASCT联合CART细胞治疗的患者PFS（P < 0.01）和OS（P < 0.01）显著更长。3级或以上免疫效应细胞相关神经毒性综合征（3级ICANS）和细胞因子释放综合征（3级CRS）事件分别发生在29%和41%的患者中。未发生治疗相关死亡。
OBJECTIVE: The objective is to explore the effectiveness and safety of CAR T-cell therapy in advanced relapsed/refractory central nervous system B-cell lymphoma and compare the impact of autologous stem cell transplantation (ASCT) plus CAR T-cell therapy versus sequential CART therapy on the survival of patients. METHODS: The retrospective analysis was based on the data of 17 patients with advanced relapsed/refractory central nervous system B-cell lymphoma. Bridging chemotherapy was applied before CAR T-cell infusion to further reduce the tumor burden. For patients with autologous hematopoietic stem cell successful collection, CD19/20/22CAR T-cell immunotherapy following ASCT was performed with the thiotepa-containing conditioning regimen, while sequential CD19/CD20/CD22CAR T-cell therapy was applied. For lymphodepletion, patients received bendamustine or fludarabine monotherapy or fludarabine combined with cyclophosphamide pre-CART-cell infusion. RESULTS: Out of the 17 patients, 8 completed ASCT plus CART cell therapy, while 9 patients completed CART cell alone therapy. In efficacy assessment at 3 months after infusion, the objective response rate (ORR) was 12/17 (71%) and the complete response rate (CRR) was 11/17 (65%). The CRR of the ASCT group and non-ASCT was 100% and 44.4%, respectively ( P < 0.01). The median progression-free survival was 16.3 (2.6-24.5) months, and the median overall survival was 19.3 (6-24.5) months. Patients who underwent ASCT plus CART cell therapy had significantly longer PFS ( P < 0.01) and OS ( P < 0.01). Grade 3 or higher immune effector cell-associated neurologic toxicity syndrome ( grade 3 ICANS) and cytokine release syndrome ( grade 3 CRS) events occurred in 29% and 41% of the patients, respectively. No treatment-related death occurred. CONCLUSION: The CAR T-cell therapy could augment its efficacy in the treatment of advanced relapsed/refractory CNS B-cell lymphoma, while ASCT in combination with CART can induce durable responses and OS with a manageable side effect.
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