摘要目的 探讨多发性骨髓瘤(MM)患者的循环骨髓瘤细胞(CMCs)数量和髓内瘤细胞(MMCs)负荷的相关性以及CMCs与MM预后相关指标的关系,评价CMCs反映骨髓瘤细胞负荷及病情进展的可行性.方法 非干预型临床研究.选择2015年7月至2016年10月于郑州大学第一附属医院确诊的82例MM患者,其中男44例,女38例,年龄58(33 ～78)岁;依据诊断和疗效标准分为初发及复发组35例、部分缓解(PR)组31例和完全缓解(CR)组16例;依据CMCs阳性标准分为CMCs阳性组45例和阴性组37例.筛选本院同期30例非浆细胞相关疾病的贫血患者作为对照组,其中男18例,女12例,年龄53 (33 ～ 83)岁.应用流式细胞术检测各组的CMCs和MMCs的比例,同时分析MM患者的血红蛋白(Hb)、血浆白蛋白(Alb)、β2微球蛋白(β2-MG)、血清肌酐(sCrea)、血清钙(Ca)、乳酸脱氢酶(LDH)、骨质破坏、肾功能损害、DS分期及ISS分期各预后相关指标.采用Kruskal-Wallis H检验、Mann-Whitney U检验、Spearman秩相关、x2检验及Logistic回归进行统计学分析.结果 (1)CR组及对照组均未检测出MMCs及CMCs.(2)初发及复发组和PR组的CMCs阳性检出率分别为71.4％、64.5％,两组中CMCs与MMCs比例均呈正相关(P ＜0.05);MMCs和CMCs在初发及复发组的比例均显著高于PR组,在PR组的比例均显著高于CR组和对照组(P ＜0.008 3).(3)与CMCs阴性组相比,CMCs阳性组的中度以上贫血、β2-MG增高、sCrea增高、骨质破坏及肾功能损害的频率明显升高,呈现出较高的DS、ISS分期(P＜0.05).经多因素Logistic回归分析,中度以上贫血、β2-MG增高是CMCs阳性的独立危险因素(P＜0.05).结论 CMCs可反映MM患者的肿瘤负荷及病情进展;相比MMCs,检测CMCs可以提高患者依从性.中度以上贫血和β2-MG增高是MM患者CMCs存在的独立危险因素.

abstractsObjective To investigate the correlation between circulating myeloma cells (CMCs)and marrow myeloma cells (MMCs) in patients with multiple myeloma (MM) and assess the feasibility of CMCs reflecting the tumor load and MM progression.Methods It is a non-intervention clinical study.Between July 2015 and October 2016,82 patients with MM from First Affiliated Hospital of Zhengzhou University were enrolled.They were divided into three groups according to the diagnosis and response criteria:newly diagnosed and relapsed group (35 cases),partial remission (PR) group (31 cases) and complete remission (CR) group (16 cases),and divided into two groups according to CMCs positive criteria:CMCs positive group (45 cases) and CMCs negative group (37 cases).Median age of the 82 MM patients(44 males,38 females) was 58 (range 33-78) years.30 patients with anemia but non-plasma cell related disorders from the same hospital in the corresponding period were screened into the control group.Median age of the 30 control subjects (18 males,12 females) was 53 (range 33-83) years.The flow cytometry was used to detect the proportions of CMCs and MMCs in each group.Other prognosis-associated factors such as hemoglobin (Hb),beta2-microglobulin (β2-MG),serumin albumin (Alb),serum creatinine (sCrea),serum calcium (Ca),lactate dehydrogenase (LDH),bone destruction,renal inadequacy,Durie-Salmon (DS) stage and international staging system (ISS) stage were simultaneously analyzed.Statistical methods including Kruskal-Wallis H test,Mann-Whitney U test,Spearman rank correlation,x2 test and Logistic regression analysis were performed.Results (1) No CMCs and MMCs were detected in CR and control group.(2) The positive detection rates of CMCs in newly diagnosed and relapsed group and PR group were 71.4％ and 64.5％ respectively.The proportions of CMCs in both groups were positively correlated with those of MMCs (P ＜ 0.05).The proportions of CMCs and MMCs in newly diagnosed and relapsed group were apparently higher than those in PR group,and the proportions of CMCs and MMCs in PR group were apparently higher than those in CR group and control group (P ＜ 0.008 3).(3) The rates of moderate to severe anemia,elevated β2-MG,elevated sCrea,bone destruction and renal inadequacy in CMCs positive group were significantly increased as compared with CMCs negative group,which led to a higher DS and ISS stage (P ＜ 0.05).The multivariate logistic regression analysis indicated that moderate to severe anemia and elevated β2-MG were independent risk factors of the presence of CMCs (P ＜ 0.05).Conclusions CMCs could reflect the tumor load and the progression of disease in patients with MM.CMCs detection could improved the patients' compliance as compared with MMCs.Moderate to severe anemia and elevated β2-MG were independent risk factors of the presence of CMCs in patients with MM.