四色流式分析多发性骨髓瘤细胞免疫表型及稳定性

目的:探讨多发性骨髓瘤(MM)细胞的免疫表型特征及稳定性。方法:用四色流式细胞术检测28例MM患者恶性浆细胞表面免疫表型,并对其中12例MM初诊患者在2～4m非单抗治疗后重复检测免疫表型。结果:与正常浆细胞不同,多数MM恶性浆细胞异常表达CD56(89.3%)、CD117(50.0%)、CD28(25%)、CD20(14.3%),不表达CD19(96.4%),近一半的患者不表达CD27(42.8%);恶性浆细胞表面免疫表型不稳定,12例初诊患者中有5例(41.67%)患者化疗后抗原表达有改变;CD38++CD45dim～-CD19-CD56+表型的恶性浆细胞所占圈定浆细胞百分率(NP)与骨髓形态学检测瘤细胞负荷有很强的正相关性(γ=0.675,P<0.01),并且可以区分稳定期和进展期患者(P<0.05)。结论:恶性浆细胞表面异常表达CD56,不表达CD19,部分表达CD117、CD28、CD20,近一半患者CD27表达缺失。部分初诊患者非单抗治疗后,恶性浆细胞表面抗原表达发生变化。NP可以稳定区分稳定期和进展期患者,是衡量病情的新指标。     

CD34抗原阳性急性非淋巴细胞白血病的临床及免疫表型特征

采用免疫荧光法检测了４３例原发性急性非淋巴细胞白血病（ＡＮＬＬ）细胞ＣＤ３４抗原及其他免疫学标记的表达，其中１３例（３０．２％）表达ＣＤ３４抗原。ＣＤ３４￣（＋）ＡＮＬＬ组在年龄、血红蛋白、白细胞、血小板、外周血和骨髓原始、幼稚细胞比例等方面与ＣＤ３４￣（－）组相比较无显著差别，但表达ＣＤ３４抗原的ＡＮＬＬ多发生在男性患者，常伴有ＨＬＡ－ＤＲ（ＤＰ）、ＣＤ３８、ＣＤ７等不成熟细胞表面标记的表达，而较成熟的髓系细胞表面标记ＣＤ１５则不表达。ＣＤ３４￣（＋）ＡＮＬＬ与ＦＡＢ亚型Ｍ１、Ｍ５ａ有着密切的关系，且对化疗反应较差，证明ＣＤ３４￣（＋）ＡＮＬＬ是一组分化程度较差的类型。     

急性淋巴细胞白血病免疫表型分析

本文对一组急性非淋巴细胞白血病检测免疫表型，分析了不同抗原的表达情况，并且对其中部分病例追踪观察化疗后的缓解情况。结果发现，本组ＡＮＬＬ化疗后不能达到完全缓解的有关因素，除多药耐药基因高度表达外，尚有ＣＤ３４抗原阳性表达，ＣＤ３３／ＣＤ１３＜１及同时表多种髓多相关抗原。     

CD7阳性急性髓细胞白血病免疫表型及临床特点

随着系列单克隆抗体的应用，白血病细胞免疫分型的广泛开展及其研究的深入，伴有ＣＤ７抗原表达的急性髓细胞白血病（ＣＤ＋７ＡＭＬ）不断被发现。有学者认为ＣＤ＋７ＡＭＬ是一类独特的急性髓细胞白血病亚型，具有与不伴有ＣＤ７抗原表达的急性髓细胞白血病（ＣＤ－７Ａ...     

急性髓细胞白血病免疫表型与预后的关系

目的分析急性髓细胞白血病免疫表型与预后的关系。方法用流式细胞术测定62例急性髓细胞白血病免疫表型。结果CD34 病例的完全缓解率明显低于CD34-组病例,差异有统计学意义(P<0.05);而难治病例发生率明显高于阴性组,差异有统计学意义(P<0.05)。Ly AML的CR率与Ly-AML组相近,而Ly AML组的难治病例发生率较Ly-AML明显增高,差异有统计学意义(P<0.05)。CD14 、CD38 、HLA-DR 各组与其阴性对照组的CR率、难治性病例发生率无统计学意义。结论CD34 AMLCR率低,难治病例发生率高,CD34是影响AML预后不良的因素。Ly AML组难治病例发生率显著高于Ly-AML,预后不良。     

骨髓增生异常综合征免疫表型分析

目的：探讨免疫表型测定在骨髓增生异常综合征（MDS）诊断及分型中的价值。方法：采用一组系列相关单克隆抗体和流式细胞术对19例MDS患者免疫表型进行检测，并对其中的10例进行了细胞遗传学检查。结果：MDS患者骨髓单个核细胞（MNC）CD13，CD33抗原表达率平均分别为36．69％和41．86％，而T淋巴系抗原CD3的表达平均仅为14．49％，且随着低危的难治性贫血（RA）向高危的难治笥贫血伴原始细胞增多（RAEB）或难治性贫血伴原始细胞增多－转变型（RAEB-t)的进展，较早期的髓系抗原CD13，CD33及干（祖）细胞抗原CD34的表达升高，并伴有T淋巴系抗原CD3的表达降低。10例进行了细胞遗传学检查的患者中，5例有染色体核型异常，染色体核型异常的患者与染色体核型正常的患者在抗原表达上存在区别。结论：对MDS患者进行免疫表型检查有助于MDS的诊断分型研究。     

急性非淋巴细胞白血病免疫表型分析

本文对一组急性非淋巴细胞白血病（ＡＮＬＬ）检测免疫表型，分析了不同抗原的表达情况，并且对其中部分病例追踪观察化疗后的缓解情况。结果发现，本组ＡＮＬＬ化疗后不能达到完全缓解的有关因素，除多药耐药基因（ＭＤＲ１、ｍＲＮＡ）高度表达外，尚有ＣＤ３４抗原阳性表达、ＣＤ３３／ＣＤ１３＜１及同时表达多种髓系相关抗原。     

流式细胞术白血病免疫表型分析的临床应用

白血病分型对选择治疗方案、判断预后都具有重要作用。应用流式细胞术(FCM)和单克隆抗体对白血病进行免疫分型的方法具有比其他免疫学方法更快速、准确、重复性好的特点。为进一步提高白血病的诊治水平，本文采用FCM检测了60例恶性血液病患者细胞免疫表型，并对各型白血病细胞抗原表达的特点和意义进行了总结和分析。     

慢性淋巴细胞白血病的临床免疫表型分析

目的评价慢性B淋巴细胞白血病(B-CLL)患者骨髓或外周血白血病细胞的免疫表型在B-CLL诊断、治疗和预后中的应用价值。方法收集26例B-CLL患者外周血或骨髓标本,应用多参数流式细胞术进行免疫表型测定。结果 26例B-CLL患者外周血淋巴细胞比例明显增加,典型的B-CLL高表达CD19、CD20、HLA-DR、cCD79a、CD5、CD23,而CD3、CD4、CD8、CD2各项指标均极度减低。结论测定B-CLL患者外周血或骨髓白血病细胞的免疫表型对于B-CLL的诊断及预后评价有重要意义。     

CD28在肾综合征出血热患者外周血T淋巴细胞免疫表型的检测及意义

肾综合征出血热(HFRS)的免疫学发病机制尚未完全阐明。近年关于HFRS患者外周血T淋巴细胞亚群及免疫表型变化的研究受到关注并取得了一定的进展[1,2]。本研究应用双色荧光单克隆抗体及流式细胞仪技术对HFRS患者外周血CD 8细胞毒性T细胞及CD28在该亚群表达的动态变化进行检测。探     

Management of multiple myeloma

Summary There has been little progress in the treatment of patients with multiple myeloma, and the average survival time is still only about 3 years. Although there have been significant therapeutic advances in recent years, clinical trials have only just begun. The major concern is, of course, the achievement of major disease control (which can be equated with a cure). The data available to date indicate that this is possible only with the use of allogeneic bone marrow transplantation, with which a survival plateau of around 30% can be attained. The trials should perhaps include the sequential use of all regimens with established efficacy in refractory myeloma. Immunoconjugate therapy with either radioisotopes or cytotoxic agents could also be envisioned, and expansion with suitable biological agents such as interleukin-2 could be considered. There is a plethora of promising treatment possibilities and novel concepts that may improve the dismal outlook for patients with multiple myeloma.Supported in part by grants CA28771 and CA37161 from the National Cancer Institute, National Institutes of Health, Bethesda, MD 20205, USA     

多发性骨髓瘤92例临床分析

目的　对多发性骨髓瘤(MM)的临床特点进行总结,为诊断和治疗提供参考。方法　对92例MM患者的临床资料进行回顾分析。结果　(1)初始化疗采用M2、VAD或MP方案有效率无显著性差异。(2)初始VAD方案化疗是否有效与患者预后相关。初治有效组和无效组中位生存期分别为43. 1个月与4. 0个月(P<0. 05)。(3)骨膦可防治骨骼进一步的破坏,但骨X线片未显示明显的骨质再钙化。化疗中加用骨膦治疗可延长患者的生存期(P<0. 05)。结论　初始VAD方案化疗有效者预后较好,中位生存期可达43. 1个月,加用骨膦治疗可延长生存期。在细胞遗传学和基因表达谱基础上行个体化治疗可能会提高疗效。     

Hyperphosphatemia in multiple myeloma

Summary We report three cases of IgG kappa multiple myeloma with pseudohyperphosphatemia. The patients' serum calcium levels were normal, and the hyperphosphatemia was not related to impaired renal function. No hypoparathyroidism was found, and no exogenous phosphate preparation had been given. Since the hyperphosphatemia was of no obvious clinical or physiological significance, as evidenced by normal serum levels of 1,25 dihydroxy vitamin D₃, it was diagnosed as spurious and was connected to interference of the paraprotein with the chromogenic assay. In two of the patients major fluctuations in serum phosphate levels were seen, induced by the changes in globulin and paraprotein levels that occurred during therapy and relapse.     

轻链型多发性骨髓瘤一例

患者,女性,61岁。因反复头昏,乏力,加重2个月入院。一年前,患者无明显诱因感头昏、乏力,伴活动后心悸,当时未行诊治。2个月前患者因受凉后出现咳嗽、咳痰,并发热,自服感冒药症状无缓解。且头昏、乏力加重,上一层楼即感心悸不适。查体:中度贫血貌,胸骨压痛,浅表淋巴结肿大,心肺(-),肝脾不大。实验室检查:Ｈｂ71ｇ/Ｌ,尿蛋白(),尿本周氏蛋白阳性;ＷＢＣ4.8×109/Ｌ,ＢＰＣ73×1012/Ｌ;ＩｇＧ6.14ｇ/Ｌ(8.00～15.50ｇ/Ｌ),ＩｇＡ0.16ｇ/Ｌ(0.74～2.86ｇ/Ｌ),ＩｇＭ0.21ｇ/Ｌ(0.62～2.26ｇ/Ｌ);抗λ血清和尿之间均出现一条明显沉淀线;尿素4.63ｍ…     

CD56与新诊断多发性骨髓瘤的预后关系分析

目的评估骨髓瘤细胞CD56表达在新诊断多发性骨髓瘤(MM)患者中的预后价值。方法选择2011年1月1日至2021年1月1日在首都医科大学北京朝阳医院治疗的332例新诊断MM患者,中位年龄为60岁,男女比例为1.2∶1,所有患者在诱导治疗前均利用流式细胞术的方法检测骨髓瘤细胞表面CD56的表达,分析骨髓瘤细胞CD56表达与新诊断MM总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)的关系。为平衡CD56阳性和阴性患者之间预后因素的分布,降低混杂因素对研究对象和结局关系的干扰,利用倾向性评分匹配技术按照1∶1比例匹配CD56阳性和阴性MM患者,用于平衡不同组别之间预后因素的分布。结果在332例患者中,216例(65.1%)患者的骨髓瘤细胞检测到CD56表达。与CD56阴性患者相比,CD56阳性患者的OS(58.4比43.1个月,P=0.024)和PFS(28.7比24.1个月,P=0.013)均明显延长。单因素Cox比例风险回归分析显示,CD56表达与更长的OS(HR=0.644,95%CI 0.438~0.947,P=0.025)及更长的PFS有关(HR=0.646,95%CI 0.457~0.913,P=0.013)。多因素分析同样证实了CD56表达是PFS的有利因素(HR=0.705,95%CI 0.497~0.998,P=0.049),但对OS却无明显影响(P>0.05)。倾向性评分匹配分析共筛选出194例患者,每组97例,CD56阳性患者PFS较长(34.2比25.1个月,P=0.047),但OS差异无统计学意义(63.4比43.1个月,P=0.056)。结论新诊断MM患者CD56表达是PFS的有利预后因素。     

Synchronous multiple myeloma and Gaucher disease

Pseudo-Gaucher cells can be found in multiple hematologic malignancies, hemoglobinopathies, infections, and multiple storage disorders upon bone marrow aspirate and biopsy; however, Gaucher disease (GD) should be ruled out, particularly when the cytoplasmic inclusions cannot be adequately characterized. It is well known that GD may be associated with monoclonal gammopathies; however, although enzyme replacement therapy (ERT) may result in an improvement in polyclonal gammopathies, its effect on the progression of monoclonal gammopathy of undetermined significance to multiple myeloma (MM) remains uncertain. ERT may improve patient’s cytopenias and facilitate administration of anti-myeloma therapy in patients with concurrent GD and MM; however, the current paucity of data makes it challenging to determine its effect on response to anti-myeloma therapy or the risk of relapse. Hematologists should be familiar with the clinical presentation and diagnosis of GD and its association with monoclonal gammopathies. Here we present a case of synchronous smoldering MM and GD.     

监测可溶性尿激酶型纤溶酶原激活物受体在预测多发性骨髓瘤患者髓外浸润及预后中的作用

目的:探讨血清可溶性尿激酶型纤溶酶原激活物受体(soluble urokinase-type plasminogen activatorreceptor,suPAR)在多发性骨髓瘤(MM)患者血清中的表达、该数值与疾病预后相关因素(分期、年龄、髓外浸润、染色体异常、肾功能、C-反应蛋白、β2-MG等)的关系及其在预测疾病预后方面的临床意义。方法:采用酶联免疫吸附的方法检测40例MM患者和30例正常对照血清suPAR表达水平。结果:①无效组与缓解组、进步组血清suPAR表达比较差异有统计学意义(P<0.05);②生存期<2年组血清suPAR表达高于生存期>2年组(P<0.01);③除血红蛋白数值高低与suPAR数值无相关性外,分期、肾功能异常、C反应蛋白、β2微球蛋白、髓外浸润各组血清suPAR值均差异有统计学意义(均P<0.05);④应用logistic回归对诸因素与患者生存期间的关系进行分析,表明疾病分期、suPAR表达水平高是导致患者生存期不足2年的独立因素。结论:suPAR水平增高与MM疾病进展、生存期缩短、早期出现髓外浸润等因素有关,提示预后不良。     

胸部CT在多发性骨髓瘤骨病变及临床预后评价中的价值

目的 探讨胸部CT在多发性骨髓瘤骨病评价中的价值以及在预后判断中的作用.方法 回顾性分析北京协和医院2010年6月至2012年8月新诊断的多发性骨髓瘤患者46例临床资料,分析其胸部CT和相应范围X线片检查、临床分期[包括Durie-Salmon (DS)分期和国际分期系统(ISS)]及其荧光原位杂交结果(显示染色体异常).结果 (1)CT和X线片对骨髓瘤骨病骨折的诊断阳性率相近,分别为41.3％ (19/46)和30.4％(14/46),差异无统计学意义(P=0.29).(2) CT较X线片对5 ～10 mm和＞10 mm溶骨性病变病例的检出率均显著提高[60.9％ (28/46)比13.0％(6/46);50.0％(23/46)比10.9％(5/46);P均＜0.001].(3)各病例中CT检出的溶骨性病变数目显著多于X线片[5 ～ 10 mm病变:5(0 ～21)处比0(0 ～4)处;＞10 mm病变:2(0 ～14)处比0(0 ～2)处;P均＜0.001].(4)CT诊断溶骨性病变阳性的患者较阴性患者的RB1基因缺失、D13s319基因缺失和高危细胞遗传学特征发生率更高[46.7％(14/30)和18.8％ (3/16);43.3％(13/30)和18.8％(3/16);50.0％(15/30)和25.0％(4/16);P均＜0.001].结论 胸部CT对评价多发性骨髓瘤溶骨病变较X线片敏感,且溶骨性病变与DS分期和RB1基因缺失、D13s319基因缺失及高危细胞遗传学特征相关,对预后判断具有一定临床意义.     

Cholesterol levels in patients with multiple myeloma

Hypocholesterolemia is seen in solid tumors and some hematological malignancies. We assessed cholesterol levels and the relationship between these levels and types and stages of multiple myeloma (MM) in the patients with MM. One-hundred two patients (60 male and 42 female) of mean age 59 ± 11 years with MM were enrolled to this study. While 71.6% of the patients were Ig G type, 80.4% of the patients were at stage III. In the control group, there were 71 healthy persons (42 male and 29 female) of mean age 58 ± 8 years. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) in the patients with MM were significantly lower than the controls (p < 0.001). There was no difference for the levels of very-low-density lipoprotein cholesterol and triglyceride between the two groups (p > 0.05). Lipid parameters were not different between Ig types (p > 0.05). The levels of TC and LDL-C in the patients with stage I were higher than those of stages II and III (p < 0.001 and p < 0.005, respectively). The levels of TC and LDL-C in the controls were not higher than the patients with stage I (p > 0.05). HDL-C levels in the patients with stage III were lower than controls (p < 0.001). Hypocholesterolemia are seen in the patients with MM. Hypocholesterolemia may be due to increased LDL clearance and utilization of cholesterol by myeloma cells. We did not receive any financial support, and this study has not been published in any journal.     

CD38‐negative relapse in multiple myeloma after daratumumab‐based chemotherapy

We present a case report of a patient relapsing after anti‐CD38 treatment (daratumumab). The phenotype of the disease changed during this treatment, and the myeloma clone became CD38 negative and daratumumab refractory. We expected clonal shift, however, based on immunophenotyping, cytogenetics and arrayCGH; the clone was identical as before daratumumab‐based treatment with the exception of CD38 negativity. We suggest that the downregulation or loss of CD38 might be an epigenetic “escape mechanism” of malignant plasma cells from antibody‐based treatment. The aim of our study was to point out the pitfalls of immunophenotyping and cytogenetics in both assessing the minimal residual disease and clone detection after monoclonal antibody‐based therapy.