Frontiers in Oncology (Oct 2021)

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
https://doi.org/10.3389/fonc.2021.741341
Journal volume & issue
Vol. 11

Abstract

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ObjectiveTo 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).MethodsWe 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.ResultsA 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.ConclusionElderly 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 Registrationhttps://www.chictr.org.cn/showproj.aspx?proj=20112.

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