双亮（CD56(bright)/CD16(bright)）扩增 NK 细胞过继性免疫治疗用于复发/难治性急性髓系白血病患者：一项概念验证研究

Patients with acute myeloid leukaemia (AML) have a five-year survival rate of 28 7%. Natural killer (NK)-cell have anti-leukaemic activity.

Here, we report on a series of 13 patients with high-risk R/R AML, treated with repeated infusions of double-bright (CD56 bright /CD16 bright ) expanded NK cells at an academic centre in Brazil. NK cells from HLA-haploidentical donors were expanded using K562 feeder cells, modified to express membrane-bound interleukin-21. Patients received FLAG, after which cryopreserved NK cells were thawed and infused thrice weekly for six infusions in three dose cohorts (10 6 -10 7 cells/kg/infusion). Primary objectives were safety and feasibility. Secondary endpoints included overall response (OR) and complete response (CR) rates at 28-30 days after the first infusion.

Patients received a median of five prior lines of therapy, seven with intermediate or adverse cytogenetics, three with concurrent central nervous system (CNS) leukaemia, and one with concurrent CNS mycetoma. No dose-limiting toxicities, infusion-related fever, or cytokine release syndrome were observed.

An OR of 78 6% and CR of 50 0% were observed, including responses in three patients with CNS disease and clearance of a CNS mycetoma. Multiple infusions of expanded, cryopreserved NK cells were safely administered after intensive chemotherapy in high-risk patients with R/R AML and demonstrated encouraging outcomes.