机构地区:[1]哈尔滨医科大学附属肿瘤医院血液淋巴内科,哈尔滨150040
出 处:《中华检验医学杂志》2022年第6期649-655,共7页Chinese Journal of Laboratory Medicine
基 金:国家癌症中心攀登基金临床研究课题(NCC201908A01);北京科创医学发展基金(KC2021-JF-0055-04,KC2021-JX-0034)。
摘 要:目的分析白细胞分化抗原分子(CD)27在多发性骨髓瘤(MM)微环境中T淋巴细胞上的表达,探讨其表达水平及CD27-/CD27+T细胞比值与骨髓瘤患者临床特征、治疗反应及预后的相关性。方法回顾性分析了2016年1月至2019年6月就诊于哈尔滨医科大学附属肿瘤医院的103例初治MM患者的资料,所有患者均接受以硼替佐米为基础的三药联合方案治疗。治疗前应用流式细胞仪检测患者骨髓标本中CD27分子在T淋巴细胞上的表达,根据CD27表达水平将MM患者分为高表达组(CD27表达≥20%)和低表达组(CD27表达<20%),比较CD27表达水平不同组间的MM临床特征、治疗反应及预后差异。统计患者生存及临床信息,分析影响MM生存的相关因素。结果103例MM患者中,CD27高表达68例(66.0%),CD27低表达35例(34.0%)。CD27高表达组中骨髓浆细胞百分比[54.4%(37/68)比22.9%(8/35),χ^(2)=9.352,P=0.002]和β2-微球蛋白(β2-MG)[58.8%(40/68)比37.1%(13/35),χ^(2)=4.348,P=0.037]显高于CD27低表达组,CD27高表达组国际分期系统(ISS)Ⅱ~Ⅲ期比例更高[79.4%(54/68)比60%(21/35),χ^(2)=4.399,P=0.036]。经4周期三药联合治疗后,CD27低表达组客观缓解率(ORR=严格意义的完全缓解+完全缓解+非常好的部分缓解+部分缓解)显著高于CD27高表达组[82.9%(29/35)比38.2%(26/68),χ^(2)=18.489,P<0.01],CD27低表达组相对治疗的深度反应率(严格意义的完全缓解+完全缓解+非常好的部分缓解)更高[48.6%(17/35)比27.9%(19/68),χ^(2)=4.326,P=0.038],且无进展生存期更长(21个月比14.1个月,t=18.655,P<0.001)。单因素分析显示CD27-/CD27+T淋巴细胞比值、ISS分期Ⅱ~Ⅲ期、年龄≥65岁、β2-MG≥3.5 mg/L、浆细胞比例≥30%均与MM患者预后有相关性,差异具有统计学意义(P<0.05)。多因素分析显示CD27-/CD27+T淋巴细胞比值是影响MM患者2年总生存期(HR=2.425,95%CI 1.216~4.835,P=0.012)和无进展生存期(HR=1.881,95%CI 1.085~3.260,P=0.024)的独立预后因素。结论MMObjective To analyze the expression of CD27 on T lymphocytes in the microenvironment of multiple myeloma(MM),and explore whether CD27 level or the CD27-/CD27+ratio of T-cell affect the prognosis of MM patients.Methods A total number of 103 newly-diagnosed MM patients from January 2016 to June 2019 were enrolled in the Affiliated Cancer Hospital of Harbin Medical University.All patients received bortezomib-based three-drugs combination regimen.The expression of CD27 on T lymphocytes in bone marrow aspirate samples was detected by flow cytometry before any treatment.MM patients were divided into two groups according to the CD27 level:CD27-high expression group(CD27 expression on T-cells≥20%)and CD27-low expression group(CD27 expression on T-cells<20%).The clinical characteristics,treatment response and prognosis of patients between the two groups were analyzed usingχ2-test.The survival and clinical information of patients were compared using Kaplan-Meier method,and the related factors related to the survival of MM were analyzed using Cox proportional risk model.Results Among 103 MM patients,68 cases(66.0%)were included in CD27 high expression group,and 35 cases(34.0%)were included in low expression group.The percentage of bone marrow plasma cells andβ2-MG level in CD27 high expression group were higher than those in CD27 low expression group significantly(54.4%[37/68]vs 22.9%[8/35],χ^(2)=9.352,P=0.002;58.8%[40/68]vs 37.1%[13/35],χ^(2)=4.348,P=0.037),and the proportion of ISS stageⅡ-Ⅲin CD27 high expression group was higher than the counterpart(79.4%[54/68]vs 60%[21/35],χ^(2)=4.399,P=0.036).After 4 cycles of three-drug combination therapy,the overall response rate(ORR=stringent complete response+complete response+very good partial response+partial response)of the low CD27 expression group was higher than the high expression group(82.9%[29/35]vs 38.2%[26/68],χ^(2)=18.489,P<0.01).The deep response rate to treatment(stringent complete response+complete response+very good partial response)was higher(48.6%[17
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