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