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51 例难治/复发 B 急性淋巴细胞白血病患者接受低剂量 CD19 导向 CAR-T 细胞治疗的高效和安全性。

High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

机构信息

Department of Hematology, Hebei Yanda Lu Daopei Hospital, Yanjiao Economic and Technological Development Zone, Langfang, China.

Department of Immunotherapy, Hebei Yanda Lu Daopei Hospital, Langfang, China.

出版信息

Leukemia. 2017 Dec;31(12):2587-2593. doi: 10.1038/leu.2017.145. Epub 2017 May 15.

Abstract

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 10/kg and were eventually settled at 1 × 10/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD patients achieved MRD. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 10/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

摘要

对于当前疗法,难治性或复发的 B 淋巴细胞白血病(B-ALL)患者的预后较差。我们用优化后的第二代 CD19 导向的 CAR-T 细胞治疗了 42 例原发性难治/血液学复发(R/R)和 9 例难治性微小残留病(MRD)的 B-ALL 患者。CAR-T 细胞输注剂量最初为 0.05 至 14×10/kg,最终为最近的 20 例患者设定为 1×10/kg。36/40(90%)可评估的 R/R 患者达到完全缓解(CR)或不完全计数恢复的 CR(CRi),9/9(100%)的 FCM-MRD 患者达到 MRD。最近的 20 例患者均达到 CR/CRi。大多数患者仅经历轻度至中度细胞因子释放综合征(CRS)。8/51 例有癫痫发作,经早期干预后缓解。23 例 CR/CRi 患者桥接异基因造血干细胞移植(allo-HCT),在中位随访时间为 206(45-427)天的情况下,仍处于 MRD 状态,而 18 例无 allo-HCT 的 CR/CRi 患者中有 9 例复发。我们的结果表明,低剂量(1×10/kg)的 CAR-T 细胞治疗难治性或复发的 B-ALL 是有效且安全的,随后进行 allo-HCT 可以进一步降低复发率。

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