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

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

doi:10.3389/fonc.2021.741341

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

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

Authors

Yan Huang¹, Minghua Hong¹, Zhigang Qu², Weiyan Zheng¹, Huixian Hu³, Linjie Li⁴, Ting Lu¹, Ying Xie¹, Shuangwei Ying⁵, Yuanyuan Zhu¹, Lizhen Liu¹, Weijia Huang¹, Shan Fu¹, Jin Chen², Kangli Wu², Mingsuo Liu², Qiulian Luo², Yajun Wu², Fang He³, Jingcheng Zhang³, Junyu Zhang⁴, Yu Chen⁴, Minlei Zhao⁴, Zhen Cai¹, He Huang¹, Jie Sun¹

Affiliations

¹ 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.
² Department of Hematology, Yiwu Central Hospital, Yiwu, China.
³ Department of Hematology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China.
⁴ Department of Hematology, The Central Hospital of Lishui City, Lishui, China.
⁵ Department of Hematology, Taizhou Hospital of Zhejiang Province, Taizhou, China.

Abstract

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% vs. 50%, P=0.002) and overall survival rates (the 1-year OS rate was 88% vs. 27%, P=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.

Keywords: HLA-mismatched CD3+ T-cell infusion; acute myelocytic leukemia; cytokine release syndrome; graft-versus-host disease; myelodysplastic syndrome.