NK细胞在异基因造血干细胞微移植治疗急性髓系白血病中的作用研究  

The Role of NK Cells in Allogeneic Hematopoietic Stem Cell Micro-Transplantation for Acute Myeloid leukemia

作　　者：刘汝玉 余长林 乔建辉 蔡博 孙琪云 王一 刘铁强 姜珊 张天耀 艾辉胜 郭梅 胡锴勋 LIU Ru-Yu;YU Chang-Lin;QIAO Jian-Hui;CAI Bo;SUN Qi-Yun;WANG Yi;LIU Tie-Qiang;JIANG Shan;ZHANG Tian-Yao;AI Hui-Sheng;GUO Mei;HU Kai-Xun(Department of Hematology and Transplantation,The Fifth Medical Center,General Hospital of the People’s Liberation Army,Beijing 100000,China;Anhui Medical University,Hefei 230000,Anhui Province,China)

机构地区：[1]解放军总医院第五医学中心血液医学部,北京100000 [2]安徽医科大学,安徽合肥230000

出　　处：《中国实验血液学杂志》2024年第2期546-555,共10页Journal of Experimental Hematology

基　　金：军队医学科技拔尖项目(20QNPY116)。

摘　　要：目的:探讨异基因造血干细胞微移植(MST)治疗急性髓系白血病(AML)患者中NK细胞的作用。方法:回顾性分析本中心2013-2018年接受MST治疗的93例AML患者的数据。诱导方案为蒽环类药物与阿糖胞苷联合粒细胞集落刺激因子动员后的外周血造血干细胞(GPBSC)输注,获得完全缓解(CR)后给予2-4个疗程的中大剂量阿糖胞苷联合GPBSC强化治疗。分析移植前未达CR的42例患者经1个疗程、2个疗程MST诱导治疗后的效果。多因素COX回归模型分析供者NK细胞数量与KIR基因型包括KIR配体错配、2DS1、单倍型和HLA-Cw配体对患者生存的影响。结果:42例患者接受MST诱导治疗1个疗程后CR率为57.1%,2个疗程后CR率为73.7%。多因素分析结果显示,中、高剂量NK细胞与患者较长的无病生存(DFS)时间显著相关(HR=0.27,P=0.005;HR=0.21,P=0.001),高剂量NK细胞与患者的较长的总生存(OS)时间显著相关(HR=0.15,P=0.000)。供者2DS1阳性显著提高患者的OS(HR=0.25,P=0.011)。对于60岁以下高危患者,供受者KIR配体错配组患者的DFS长于非错配组(P=0.036);供者2DS1阳性显著延长患者的OS(P=0.009)。结论:NK细胞剂量、KIR配体错配与2DS1能够影响MST的治疗效果,改善AML患者的生存。Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1%after 1 course and 73.7%after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

关 键 词：急性髓系白血病 造血干细胞 微移植 NK细胞 KIR 

分 类 号：R733.71[医药卫生—肿瘤]