High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients
High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients
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DOI：
10.1038/leu.2017.145
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发表时间：
2017-12-01
期刊：
影响因子：
11.4
通讯作者：
Tong, C. R.
中科院分区：
文献类型：
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作者：
Pan, J.;Yang, J. F.;Tong, C. R.
难治性或复发性B淋巴母细胞白血病（B-ALL）患者目前的治疗结果令人沮丧。我们用优化的第二代CD 19导向的CAR-T细胞治疗了42例原发性难治性/血液学复发（R/R）和9例难治性微小残留病（FCM-MRD+）B-ALL患者。CAR-T细胞输注剂量最初范围为0.05至14 x 10（5）/kg，最近20例病例最终确定为1 x 10（5）/kg。36/40例（90%）评价的R/R患者达到完全缓解（CR）或CR伴计数不完全恢复（CRi），9/9例（100%）FCM-MRD+患者达到MRD-。最近20例患者均达到CR/CRi。大多数病例仅发生轻度至中度CRS。8/51例病例的癫痫发作通过早期干预缓解。27例过渡到异基因造血干细胞移植（allo-HCT）的CR/CRi患者中有23例仍处于MRD状态，中位随访时间为206（45-427）天，而18例未接受allo-HCT的CR/CRi患者中有9例复发。我们的研究结果表明，1 × 10（5）/kg的低CAR-T细胞剂量对于治疗难治性或复发性B-ALL是有效和安全的，随后的allo-HCT可以进一步降低复发率。
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 x 10(5)/kg and were eventually settled at 1 x 10(5)/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 x 10(5)/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.