AUTHOR=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 

TITLE=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

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.741341

DOI=10.3389/fonc.2021.741341

ISSN=2234-943X

ABSTRACT=<sec><title>Objective</title><p>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).</p></sec><sec><title>Methods</title><p>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<sup>+</sup> 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.</p></sec><sec><title>Results</title><p>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% <italic>vs.</italic> 50%, <italic>P</italic>=0.002) and overall survival rates (the 1-year OS rate was 88% <italic>vs.</italic> 27%, <italic>P</italic>=0.014). Post-TLI cytokine-release syndrome (CRS) occurred after 79% of allo-TLI operations, and 96% of CRS reactions were grade 1.</p></sec><sec><title>Conclusion</title><p>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.</p></sec><sec><title>Clinical Trial Registration</title><p><uri xlink:href="https://www.chictr.org.cn/showproj.aspx?proj=20112" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.chictr.org.cn/showproj.aspx?proj=20112</uri>.</p></sec>