Carfilzomib associated thrombotic microangiopathy initially treated with therapeutic plasma exchange

Drug associated thrombotic microangiopathy (TMA) is a rare event causing thrombocytopenia, microangiopathic anemia, renal failure, and neurologic abnormalities. Here, we present a case of TMA that occurred during the first cycle of treatment with carfilzomib for relapsed multiple myeloma. J. Clin. Apheresis, 2014. © 2014 Wiley Periodicals, Inc.     

Flavopiridol联合Bortezomib对多发性骨髓瘤的细胞增殖抑制作用

目的探讨细胞蛋白激酶抑制剂Flavopiridol及蛋白酶抑制剂Bortezomib在体内抑制多发性骨髓瘤细胞U266的细胞增殖作用及其机制。方法以不同浓度的Flavopiridol及Bortezomib分别、联合作用于U266细胞,用MTT法检测细胞增殖抑制作用。采用western blot法检测Bcl-2及Mcl-1表达变化;结果①Flavopiridol比Borte-zomib对U266细胞增殖抑制作用更强,IC50值分别为52.5nM,25nM。②与单独用药相比,Flavopiridol联合Borte-zomib作用于U266细胞,IC50值有明显的下降为17.5nM。③Flavopiridol及Bortezomib给药前后,Bcl-2蛋白表达无变化,而Mcl-1蛋白表达明显下降。结论 Flavopiridol联合Bortezomib用药能在体内明显抑制多发性骨髓瘤细胞U266的生长,其机制主要是通过诱导细胞凋亡来抑制增殖。     

Meningeal involvement in multiple myeloma

A patient with multiple myeloma with a mass in the nasopharyngeal was diagnosed. He received melphalan autograft and radiotherapy, and obtained complete remission. He relapsed 3 months later, with meningeal involvement and without systemic relapse. He received intrathecal and systemic chemotherapy, without neurological improvement and died 4 weeks after relapse.     

蛋白酶体抑制剂对多发性骨髓瘤患者骨髓间充质干细胞迁移能力及其肝细胞生长因子表达的影响

本研究探讨蛋白酶体抑制剂硼替佐米对多发性骨髓瘤(MM)患者骨髓间充质干细胞(MSC)迁移能力及其肝细胞生长因子(HGF)基因表达水平的影响。应用Transwell模型观察MM患者骨髓MSC经2.5 nmol/L硼替佐米处理前后的体外迁移能力,实时定量PCR检测MSC的HGF mRNA的表达水平。结果表明,经2.5 nmol/L的硼替佐米作用48小时后,MSC的迁移能力明显低于对照组,并且HGF mRNA在MSC的表达与对照组相比也明显降低,两者结果均具有统计学意义(p<0.05)。结论:硼替佐米可抑制MM患者骨髓MSC的迁移,同时可下调其趋化相关因子HGF的表达。     

Proteasome 20S in multiple myeloma: comparison of concentration and chymotrypsin-like activity in plasma and serum

The ubiquitin-proteasome system is relevant in the pathobiology of many haematological malignancies, including multiple myeloma. The assessment of proteasome concentration and chymotrypsin-like (ChT-L) activity might constitute a new approach to diagnosis, prognosis and monitoring of anticancer treatment of patients with haematological malignancies and other diseases. The aim of our study was to determine which material, plasma or serum, is better for measuring chymotrypsin-like (ChT-L) activity and proteasome concentration. We analysed proteasome concentration and chymotrypsin-like (ChT-L) activity in 70 plasma and serum samples drawn from 28 patients at different treatment stages for multiple myeloma (MM) and 31 healthy volunteers. Proteasome ChT-L activity and concentration in multiple myeloma patients were significantly higher in plasma compared to serum. In this group we observed significant and positive correlations both between the plasma and serum proteasome ChT-L activity and plasma and serum proteasome concentration. The higher values of proteasome concentration and ChT-L activity in plasma than in serum and their better correlations with parameters of tumour load and prognosis suggest that plasma constitutes a better biological material for measuring ChT-L activity and proteasome concentration than serum in multiple myeloma patients.     

蛋白酶体抑制剂硼酸盐二肽治疗难治性多发性骨髓瘤

多发性骨髓瘤是中老年人群常见且不能治愈的一种恶性肿瘤,蛋白酶体抑制剂硼酸盐二肽主要通过作用于NF-κB而影响黏附分子表达、抑制血管生成、促进瘤细胞凋亡、降低IL-6等细胞因子分泌达到选择性杀伤骨髓瘤细胞目的。本研究报道了硼酸盐二肽对2例复发难治性多发性骨髓瘤的临床治疗情况。病例1为多发性骨髓瘤,IgA型,ⅢA期的复发难治性病例,在自体外周血干细胞移植后8个月出现病情复发进展,先后给予多种药物组成的联合化疗方案治疗4个疗程,病情呈侵袭性进展,表现为骨髓中骨髓瘤细胞增加,血浆异常单克隆免疫球蛋白增高和骨骼破坏加重,并出现肋骨浆细胞瘤。给予硼酸盐二肽联合柔红霉素、地塞米松、沙利度胺的VADT方案治疗1个疗程获得显著疗效,表现为血浆IgA由54g/L降至6.6g/L,骨髓异常浆细胞由治疗前40%降至0.6%,患者右侧前上胸壁外侧5cm×6cm骨骼包块在治疗后基本消散;但第2个疗程VADT方案治疗无效并再次出现病情进展。病例2为多发性骨髓瘤,轻链kappa型,ⅢB期的原发难治性患者,先后2个疗程VAD和1疗程MOFP方案化疗无效;在VADT方案治疗1个疗程后即获得显著疗效,尿kappa由24-30g/24h降至1.12g/24h,血肌酐由475.3μmol/L降至124.2μmol/L,β2微球蛋白由1.61mg/dl降至0.64mg/dl;第3疗程后尿kappa定量降至0.088g/24h,β2-MG、LDH和白蛋白水平均在正常范围,获完全缓解。病例1主要不良反应有明显疲乏无力,水样腹泻,四肢指趾端轻微发麻发木,均可耐受,并经对症处理及停用治疗后逐渐消失。病例2的主要并发症为第1疗程第3次用药时硼酸盐二肽剂量增加为1.45mg/m2后出现严重的亚急性左侧肢体偏身运动障碍,发病第2天最为严重,左侧上肢近端肌力1级,远端0级,左下肢2级,2周以后肌力逐渐恢复至正常;本例患者无疲乏、血小板减少等并发症。结论硼酸盐二肽是一个靶向性治疗多发性骨髓瘤的有效药物,但作为一种新药需注意加强不良反应的观察,及时处理可能出现的并发症。     

Long‐term survival in multiple myeloma

The survival of multiple myeloma patients has improved very significantly over the last decade. Still median overall survival is inferior to 5 years. A small proportion of patients survive longer than 10 years. In this paper we discuss four cases illustrating the nonhomogeneous clinical presentation and evolution of this subset of patients. Surprisingly, these long survivors do not always have deep responses and some require frequent treatments, which include autologous stem cell transplantation and novel drugs. The authors discuss several aspects of these clinical histories, including treatment options, raising hypothesis on their relation with long survivorship which may be important to have in consideration when studying this subject.     

蛋白酶体抑制剂对白血病作用的研究进展

蛋白酶体负责细胞内蛋白的降解,其活性的异常改变是肿瘤发生的标志。研究证实,蛋白酶体抑制剂对许多恶性肿瘤有抗癌活性,第一个获准临床试验和上市的蛋白酶体抑制剂硼替佐米治疗多发性骨髓瘤患者获得了较高的总体有效率和完全缓解率。国外学者也开展了一系列蛋白酶体抑制剂对白血病细胞治疗作用的研究,本文就蛋白酶体抑制剂对浆细胞白血病、慢性淋巴细胞白血病、成人T细胞淋巴瘤/白血病、慢性髓系白血病、急性髓系白血病作用的研究进展作一综述。     

多发性骨髓瘤的过去、现在及未来

多发性骨髓瘤是一种浆细胞系恶性肿瘤，依靠传统的化疗方案不能够治愈。近年来，基于对骨髓瘤生物学、遗传学以及肿瘤发生学的深入研究，开发研制出一些新药，并提出了靶向治疗的新方法，如利用蛋白酶体抑制剂、免疫调节剂等，能够极大的改善病人的预后；另外，新的联合化疗方案的出现，也明显提高了缓解率。这些新的治疗策略为临床工作带来了巨大帮助，本文对治疗多发性骨髓瘤的新看法的最近进展进行了评述。     

多发性骨髓瘤免疫表型研究进展

多发性骨髓瘤(MM)是一种克隆性的B细胞疾病,以恶性浆细胞(PC)在骨髓中大量增殖,产生溶骨性破坏及过量单克隆免疫球蛋白为主要表现。MM的诊断主要依靠骨髓中存在浆细胞浸润,血、尿中存在一定量的单克隆蛋白以及瘤细胞浸润或单克隆蛋白引起的器官损害(高钙血症、肾功能不全、贫血、骨质破坏等)。本文就流式细胞术免疫表型检测对MM诊断和预后意义的研究进展做一综述。     

Heat insoluble cryoglobulin associated with gangrene in multiple myeloma

Cryoglobulins are immunoglobulins that have tendency to precipitate in temperatures below 37 degrees C and dissolve with rewarming. Monoclonal cryoglobulins are usually associated with a distinct hematological disorder and often are asymptomatic. Heat insoluble cryoglobulin has been described with Sjogren's syndrome and glomerulonephritis but, not with multiple myeloma. Severe sensitivity to cold occurs with high thermal insolubility of the cryoprotein, with dramatic symptoms when exposed to minimal lowering of the temperature. We report a case of a 49 year old man with multiple myeloma and an unusual type I cryoglobulin that caused occlusive gangrene. The cryoglobulin appeared as a milky white precipitate that was resistant to re-suspension and did not dissolve at 37 degrees C. Immunoelectrophoresis of the cryoglobulin, which dissolved at 56 degrees C, showed it to be composed of a monoclonal IgG kappa protein (3.5 g/dl). Unlike most high thermal insoluble cryoglobulin, cold associated symptoms were not seen. In addition to steroids, plasmapheresis was initiated thrice a week with albumin fluid replacement. Plasmapheresis caused a marked decline in cryocrit levels from 21% to less than 0.5% in 9 days after 4 procedures with resolution of the gangrene of the feet and after 6 treatments, vasculitic symptoms improved dramatically. The cryoglobulin test was negative 2 weeks after initiation of treatment. The patient was treated for the myeloma and there was no recurrence of occlusive symptoms. Proper laboratory procedure and careful examination and handling of cryoglobulinemic samples facilitate detection of unusual cryoglobulins. This is a unique report of multiple myeloma with gangrene of lower extremities that has a heat insoluble cryoglobulin.     

NT-proBNP在多发性骨髓瘤诊断中的应用研究

目的研究血清N端前脑钠肽(NT-proBNP)水平在多发性骨髓瘤中的诊断价值。方法收集整理徐州医科大学附属医院2017年12月至2018年12月门诊及住院明确诊断为多发性骨髓瘤并同时检测了M蛋白和血清NT-proBNP的患者共132例,并将收集的132例按NT-proBNP值分低值、中值、高值3个小组,另外收集同时检测了M蛋白和血清NT-proBNP的健康体检者132例作为健康对照组。用SPSS18.0软件通过箱体图、秩和检验和ROC曲线对相应数据进行分析统计。结果多发性骨髓瘤患者低值、中值、高值3组NTproBNP水平都高于健康对照组,组间差异均有统计学意义(P<0.01)。以M蛋白电泳为金标准,分析NTproBNP对多发性骨髓瘤的诊断价值,做ROC曲线,其ROC曲线下面积为0.899,NT-proBNP最佳诊断临界值为1 381.0pg/mL,用该值诊断多发性骨髓瘤的灵敏度为76.9%,特异度为84.6%。结论 NT-proBNP在多发性骨髓瘤辅助诊断中具有重要的临床意义,且通过ROC曲线分析,可以发现其诊断多发性骨髓瘤的灵敏度、特异度较高,为多发性骨髓瘤的诊断提供另一种简单的有效途径。     

多发性骨髓瘤的治疗现状和规范

多发性骨髓瘤(MM)是一种异常浆细胞过度增殖的恶性肿瘤,传统化疗效果不佳,完全缓解率(CR)＜10％,中位生存期仍然只有33个月左右.自体造血干细胞移植(ASCT)的应用改善了MM的疗效,含新药的诱导化疗能达到与移植相似的疗效.目前认为,含新药的诱导治疗序贯ASCT是≤65岁适合移植的初治MM患者的治疗策略,单次移植后疗效≥非常好的部分缓解的患者不需要二次移植.移植后的巩固和维持治疗是有益的.对于＞65岁及不适合移植的初治MM患者,含新药的诱导治疗和维持治疗同样是合适的.     

多参数流式细胞术测定多发性骨髓瘤细胞免疫标记的研究

本研究探讨多发性骨髓瘤(MM)的免疫表型特征及其意义。采用多参数流式细胞术直接免疫荧光技术,CD38/SSC设门,对33例MM患者及12例浆细胞反应性增多症患者的骨髓标本进行免疫分型检测,并辅以瘤细胞的形态学检查。结果表明:形态学检查观察到瘤细胞比例为6.0%-76.0%;流式细胞术CD38/SSC设门后可见到一群CD38强阳性细胞,比例为0.99%-57.54%;多数MM细胞表型为CD38st+CD138+CD19-CD56+(78.8%),部分患者伴有CD20(12.1%)、CD33(15.2%)、CD117(30.3%)、HLA-DR(9.1%)抗原表达,其余抗原表达均为阴性;27例(81.8%)MM患者检测到cκ或cλ的单克隆限制性,其余cκ及cλ均为阴性。结论:利用CD38/SSC设门方法的流式细胞术对MM进行免疫分型,根据细胞表面抗原的异质性,可鉴别良性或恶性浆细胞,为判断预后及靶向治疗提供依据。     

兰州地区多发性骨髓瘤患者M蛋白免疫固定电泳结果分析

目的 分析兰州地区多发性骨髓瘤患者M蛋白在年龄、性别方面的型别特征.方法 对兰州地区144例多发性骨髓瘤患者M蛋白进行免疫固定电泳分析.结果 从性别上看,男性发病率为女性的1.36倍,IgG-κ＞λ,IgA-λ＞κ;女性患者中IgG型和IgA型均为λ＞κ.发病年龄多为50～70岁,70～80岁次之,35岁以下未见,＞80岁者亦少见.结论 兰州地区多发性骨髓瘤发病在性别、M蛋白型别方面具有其特征.     

116例多发性骨髓瘤免疫特征表型分析

目的了解多发性骨髓瘤(MM)的免疫表型特征,以及CD45、CD19与临床特征的相关性。方法采用三色流式细胞术对116例初诊MM病例进行免疫表型分析,并收集患者的实验室和临床指标。结果 116例MM均表达CD38,其他抗原CD19、CD138、CD56、CD20、CD33、CD117、CD45的阳性率分别为10.3%、96.6%、60.7%、3.4%、70.0%、25.6%、17.2%,无1例表达CD7、CD34。在116例MM中,胞浆κ轻链阳性率为34.5%,λ轻链阳性率为48.3%。CD45阳性患者分期较好,其表达缺失患者易出现骨破坏,微球蛋白、C反应蛋白水平较高;CD19表达与高分期有关,易出现贫血,微球蛋白、C反应蛋白水平较高。结论了解MM的免疫表型特点对此类疾病的诊断具有重要意义,其中CD45、CD19与分期等临床生物学特征有关,有助于判断预后。     

Cutaneous involvement in relapsed multiple myeloma

Cutaneous involvement in multiple myeloma with extramedullary disease is rare. We report the case of a refractory multiple myeloma patient who developed a cutaneous lesion. Histopathology revealed dermal immature plasma cell infiltrate with a lack of CD138 expression. This cutaneous location was associated with an aggressive clinical course and short survival.