非清髓性化疗后输注HLA配型不合的异基因CD3 T细胞导致T细胞扩增并伴有轻度细胞因子释放综合征：一项针对老年急性髓系白血病和int-2/高危骨髓增生异常综合征患者的多中心单臂前瞻性研究。

Non-Ablative Chemotherapy Followed by HLA-Mismatched Allogeneic CD3 T-Cells Infusion Causes An Augment of T-Cells With Mild CRS: A Multi-Centers Single-Arm Prospective Study on Elderly Acute Myeloid Leukemia and int-2/High Risk Myelodysplastic Syndrome Patients.

作者信息

Huang Yan, Hong Minghua, Qu Zhigang, Zheng Weiyan, Hu Huixian, Li Linjie, Lu Ting, Xie Ying, Ying Shuangwei, Zhu Yuanyuan, Liu Lizhen, Huang Weijia, Fu Shan, Chen Jin, Wu Kangli, Liu Mingsuo, Luo Qiulian, Wu Yajun, He Fang, Zhang Jingcheng, Zhang Junyu, Chen Yu, Zhao Minlei, Cai Zhen, Huang He, Sun Jie

机构信息

Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy; Zhejiang Laboratory for Systems & Precison Medicine, Zhejiang University Medical Center, Institute of Hematology, Bone Marrow Transplantation Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Department of Hematology, Yiwu Central Hospital, Yiwu, China.

出版信息

Front Oncol. 2021 Oct 13;11:741341. doi: 10.3389/fonc.2021.741341. eCollection 2021.

OBJECTIVE

To evaluate the efficacy and safety of standard or low-dose chemotherapy followed by HLA-mismatched allogeneic T-cell infusion (allo-TLI) for the treatment of elderly patients with acute myeloid leukemia (AML) and patients with intermediate-2 to high-risk myelodysplastic syndrome (MDS).

METHODS

We carried out a prospective, multicenter, single-arm clinical trial. Totally of 25 patients were enrolled, including 17 AML patients and 8 MDS patients. Each patient received four courses of non-ablative chemotherapy, with HLA-mismatched donor CD3 allo-TLI 24 h after each course. AML patients received chemotherapy with decitabine, idarubicin, and cytarabine, and MDS patients received decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor.

RESULTS

A total of 79 procedures were performed. The overall response rates of the AML and MDS patients were 94% and 75% and the 1-year overall survival rates were 88% (61-97%) and 60% (13-88%), respectively. The overall 60-day treatment-related mortality was 8%. Compared with a historical control cohort that received idarubicin plus cytarabine (3 + 7), the study group showed significantly better overall response (94% 50%, =0.002) and overall survival rates (the 1-year OS rate was 88% 27%, =0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1.

CONCLUSION

Elderly AML patients and intermediate-2 to high-risk MDS patients are usually insensitive to or cannot tolerate regular chemotherapies, and may not have the opportunity to undergo allogeneic stem cell transplantation. Our study showed that non-ablative chemotherapy followed by HLA-mismatched allo-TLI is safe and effective, and may thus be used as a first-line treatment for these patients.

CLINICAL TRIAL REGISTRATION

https://www.chictr.org.cn/showproj.aspx?proj=20112.

目的

评估标准剂量或低剂量化疗后进行人类白细胞抗原（HLA）配型不合的异基因T细胞输注（allo - TLI）治疗老年急性髓系白血病（AML）患者及中2至高危骨髓增生异常综合征（MDS）患者的疗效和安全性。

方法

我们开展了一项前瞻性、多中心、单臂临床试验。共纳入25例患者，其中17例AML患者和8例MDS患者。每位患者接受四个疗程的非清髓性化疗，每个疗程后24小时进行HLA配型不合供者CD3 allo - TLI。AML患者接受地西他滨、伊达比星和阿糖胞苷化疗，MDS患者接受地西他滨、阿糖胞苷、阿克拉霉素和粒细胞集落刺激因子治疗。

结果

共进行了79次操作。AML和MDS患者的总缓解率分别为94%和75%，1年总生存率分别为88%（61 - 97%）和60%（13 - 88%）。60天总体治疗相关死亡率为8%。与接受伊达比星加阿糖胞苷（3 + 7）的历史对照队列相比，研究组的总缓解率（94%对50%，P = 0.002）和总生存率（1年总生存率为88%对27%，P = 0.014）显著更好。79%的allo - TLI操作后发生TLI后细胞因子释放综合征（CRS），96%的CRS反应为1级。