A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia
A retrospective comparison of allogenic and autologous chimeric antigen receptor T cell therapy targeting CD19 in patients with relapsed/refractory acute lymphoblastic leukemia
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针对 CD19 的同种异体和自体嵌合抗原受体 T 细胞治疗复发/难治性急性淋巴细胞白血病患者的回顾性比较
DOI：
10.1038/s41409-018-0403-2
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发表时间：
2019-08-01
影响因子：
4.8
通讯作者：
Huang, He
中科院分区：
文献类型：
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作者：
Hu, Yongxian;Wang, Jiasheng;Huang, He
CAR - T细胞的来源可以是自体（autoCAR）或同种异体（alloCAR）。后者见于有同种异体造血干细胞移植史的患者，可以是供体来源（DD-alloCAR）或受体来源（RD-alloCAR）。autoCAR仅被CAR激活，而alloCAR同时接受t细胞受体（TCR）和CAR的激活信号。因此，生物学上的差异可能会影响临床结果。我们回顾性分析了31例患者：17例接受autoCAR， 11例接受RD-alloCAR， 3例接受DD-alloCAR。中位随访9个月后，autoCAR的CR率为88.2% (95% CI 63.6-98.5%)， RD-alloCAR的CR率为100% （95% CI 71.5-100%）。autoCAR组的中位峰扩张显著高于RD-alloCAR组（p= 0.007）。RD-alloCAR组发生严重CRS（≥3级）的患者明显少于autoCAR组（p= 0.049）。急性移植物抗宿主病（GVHD）发生在2例（18.2%）RD-alloCAR患者和1例（33.3%）DD-alloCAR患者中。alloCAR组的单变量亚组分析显示，收集t细胞时cGVHD的存在与小于6个月的复发显著相关（p= 0.022）。在PBMC收集时伴有或不伴有cGVHD的RD-alloCAR患者在CAR - t细胞扩增峰值、CRS分级和OS方面没有差异。
The source of CAR T cells can be autologous (autoCAR) or allogeneic (alloCAR). The latter is seen in patients with a history of allogeneic hematopoietic stem cell transplantation, and can be either donor-derived (DD-alloCAR) or recipient-derived (RD-alloCAR). While autoCAR is activated by CAR only, alloCAR receives activation signals from both T-cell receptor (TCR) and CAR. As a result, the biological differences could impact clinical outcomes. We retrospectively reviewed 31 patients: 17 received autoCAR, 11 received RD-alloCAR, and 3 received DD-alloCAR. After a median follow-up of 9 months, CR rate was 88.2% (95% CI 63.6–98.5%) in autoCAR and 100% (95% CI 71.5–100%) in RD-alloCAR. The median peak expansion in the autoCAR was significantly higher than the RD-alloCAR group (p= 0.007). RD-alloCAR group had significantly less patients with severe CRS (Grade ≥ 3) than the autoCAR group (p= 0.049). Acute graft-versus-host disease (GVHD) occurred in 2 (18.2%) of RD-alloCAR patients and 1 (33.3%) of DD-alloCAR patients. Univariate subgroup analysis of alloCAR group showed the presence of cGVHD at the time of T-cell collection was significantly associated with less than 6-month relapses (p= 0.022). RD-alloCAR patients with or without cGVHD at PBMC collection did not differ regarding the peak CAR T-cell expansion, CRS grades and OS.