M蛋白定量在诊断和治疗多发性骨髓瘤中的临床意义

 目的 分析M蛋白定量在多发性骨髓瘤（MM）的诊断和治疗中的临床意义。方法 回顾性分析70例MM患者的临床资料与M蛋白之间的关系,并进行统计学分析。结果 初治时IgG、IgA型 M蛋白的量与MM细胞的负荷均呈正相关（r = 0.550,P＜0.05;r = 0.765,P＜0.05）,初治时IgG、IgA及轻链型M蛋白的量与血红蛋白计数呈负相关（r = -0.462,r = -0.744,r = -0.638,P＜0.05）;M蛋白的量与初治时患者的骨质破坏程度无明显相关;肾功能不全的发生率在IgG型（21.2 %）低于IgA型（58.9 %）及轻链型（53.3 %）,三者之间相比差异有统计学意义（P＜0.05）;化疗2个疗程后M蛋白的下降与初治时M蛋白的量无明显相关;传统化疗总有效率低（53.8 %）。结论 M蛋白是MM诊断和临床分期的重要指标,也是评价治疗是否有效的标准之一,目前的化疗方案总体缓解率低。     

多发性骨髓瘤患者血清胆固醇水平的临床意义

 目的　探讨多发性骨髓瘤（MM）患者血清胆固醇水平变化及其与分型、分期的关系。方法　回顾分析65例MM患者诊断时血脂水平,包括总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、载脂蛋白A1（Apo-A1）和载脂蛋白B（Apo-B）,探讨血脂参数与MM患者免疫球蛋白类型和临床分期关系。以健康体检者30例作为对照组。结果　65例MM患者中IgG型35例（53.85 %）,Ⅲ期41例（63.1 %）,MM患者血清TC、HDL-C、 LDL-C、Apo-A1和Apo-B明显低于对照组 （P＜0.05）,两组TG差异无统计学意义（P＞0.05）;除1例IgD型外,其余64例患者中,IgG和IgA型患者血清TC、HDL-C、LDL-C、Apo-A1和Apo-B均显著低于轻链型（P＜0.05）,TG水平在不同Ig类型患者间无差别;Ⅲ期患者血清TC、HDL-C、LDL-C和Apo-A1均显著低于Ⅰ期患者和对照组（P均＜0.05）,且Ⅱ期患者血清LDL-C 也显著低于Ⅰ期患者（P＜0.05）。结论　MM患者存在低胆固醇血症,且血清胆固醇水平与疾病分期有关。     

双克隆型多发性骨髓瘤五例

 目的　研究双克隆型多发性骨髓瘤（MM）患者的临床特点及治疗。方法　分析该科自1996年1月至2010年6月收治的5例双克隆型MM患者,男性2例,女性3例,年龄59～76岁,中位年龄72岁。其中IgG+IgA型3例,IgM+IgG／A型2例。结果　本组患者中诊断时均为DS分期Ⅲ期,治疗效果为2／4达到部分缓解（PR）,1／4为稳定（SD）,1／4为进展（PD）,无达到完全缓解（CR）的病例。结论　双克隆型MM较为罕见,目前对此型MM的诊断和治疗尚缺乏更深刻的认识,需要更多病例的分析。     

多发性骨髓瘤患者M蛋白标记的临床意义

目的:探讨多发性骨髓瘤（multiple myeloma,MM）患者血清蛋白电泳M蛋白标记的临床意义,观察其定量水平监测疾病进展和评估治疗药物的疗效。方法:对169例患者血清蛋白电泳的M蛋白波峰进行柱状法标记,通过免疫固定电泳(IFE)确诊其免疫分型,同时进行血清总蛋白（TP）、白蛋白(ALB)含量检测。连续追踪25例初诊诊断为MM患者的血清蛋白电泳,将M蛋白波峰标记得到M 蛋白百分比,换算M 蛋白浓度。换算公式:M 蛋白浓度（g/L）=TP浓度（g/L）×M蛋白百分比（%）,将计算结果进行对比。结果:在169例患者中,血清蛋白电泳β区见M蛋白波峰49例（29.0%）、γ区见M蛋白波峰120例（71.0%）,经过IFE分型:κ型IgG 型48例(28.4%),λ型IgG型43例(25.4%);κ型IgA型14例(8.3%),λ型IgA型16例(9.5%);κ型IgM 11例(6.5%),λ型IgM 3例(1.8%);κ型IgD型 2例(1.2%),λ型IgD型6例(3.6%); 游离κ轻链型2例(1.2%),游离λ轻链型8例(4.7%);双克隆型 1例(0.6%);未见单克隆条带15例(8.9%)。随访和监测25例MM患者化疗疗效评估:化疗后较化疗前白蛋白明显升高;其中β区M蛋白4例,β球蛋白及M蛋白浓度明显降低,差异均有统计学意义（P＜0.05）;γ区M蛋白21例,γ球蛋白及M蛋白显著降低（P＜0.05、P＜0.01）,其中M蛋白持续存在的MM患者,第1次评估血清TP含量和M 蛋白浓度明显下降、ALB含量明显升高,第2次评估TP、ALB含量在正常参考值区间,趋于平稳,M 蛋白浓度逐渐下降,可至消失。结论:血清蛋白电泳M蛋白的标记是诊断MM、巨球蛋白血症、淀粉样变等浆细胞病的依据,可作为标志物对其定量,更好的为监测疾病进展和评估治疗药物的疗效提供指导。     

血清唾液酸在IgA型多发性骨髓瘤诊断和治疗中的临床意义

目的 探讨血清唾液酸(SA)在IgA型多发性骨髓瘤(MM)诊断及治疗中的临床意义.方法 应用生化免疫分析仪测定50名健康体检者及76例MM患者确诊时及治疗后的血清SA水平.结果 76例MM中,IgA型25例,除IgA型外51例(IgG型40例,轻链型7例,不分泌型4例).健康对照及IgA型、IgG型、轻链型、不分泌型、除IgA型外MM患者确诊时血清SA平均水平分别为(570.33±67.72)、(1289.24±325.42)、(585.88±159.12)、(600.77±126.90)、(590.50±100.86)、(588.39±150.90)mg/L,IgA型MM患者血清SA水平高于健康对照及其他各型MM(均P<0.01),而健康对照及其他各型MM间血清SA水平差异无统计学意义(均P>0.05).IgA型MM患者确诊时血清SA水平与血清IgA、球蛋白、骨髓涂片浆细胞数、红细胞沉降率呈正相关(r值分别为0.699、0.753、0.504、0.732,均P<0.05),与血清清蛋白、IgG、血红蛋白、血小板呈负相关(r值分别为-0.712、-0.505、-0.629、-0.596,均P<0.05),与白细胞、血清肌酐、血清IgM、乳酸脱氢酶、血清钙、C反应蛋白、β2微球蛋白不相关(均P>0.05).IgA型MM患者血清SA水平随病情好转而下降,随病情加重而上升.结论 IgA型MM患者血清SA升高,是反映IgA型MM肿瘤负荷量的指标,也可作为其疗效评价的指标.     

43例轻链型多发性骨髓瘤临床分析

多发性骨髓瘤(MM)是恶性浆细胞病中最常见的一种类型,按免疫学分类可分为IgG、IgA、IgD和轻链型等类型,其中轻链型可占15%～20%,此型瘤细胞仅合成和分泌单克隆轻链,瘤细胞常分化较差,骨骼破坏及肾功能损害较重,预后较差.为提高对该病的认识,我们回顾性总结了近13年来我院初治的轻链型MM患者43例,对其临床特点进行分析.     

肿瘤患者血脂与相位角、体脂百分比的相关性分析

目的:分析肿瘤患者血脂水平的影响因素以及血脂与相位角（PA）、体脂百分比（PBF）的相关性,为肿瘤患者营养管理和研究方向提供参考。方法:收集2020年12月至2022年04月我院收治的159例肿瘤患者一般临床资料、患者主观整体营养评估量表（PG-SGA）评分、用药史、既往病史、个人史、入院后血脂、人体成分分析结果。通过比较不同临床特征患者血脂水平和PBF的差异,血脂、PG-SGA评分与PA、PBF之间的相关性,分析肿瘤患者血脂与PA、PBF之间的关联和影响。结果:不同瘤种之间甘油三酯（TG）和PBF存在差异（P＜0.05）;女性、低龄和行为状况（PS）评分低的患者,总胆固醇（TC）、TG要高于男性、高龄和PS评分高的患者（P＜0.05）,吸烟患者有更低TG和载脂蛋白A（Apo-A）（P＜0.05）,饮酒患者高密度脂蛋白（HDL）更低（P＜0.05）。中度营养不良患者TC和低密度脂蛋白（LDL）水平最低（P＜0.05）,TG随着营养状态恶化单调下降。将抗肿瘤治疗措施按血脂异常的风险进行分组比较,各风险组未见血脂水平存在差异。PA与PG-SGA呈显著负相关（r=-0.425,P＜0.001）,与TC、TG、LDL呈正相关（P＜0.05）。PBF与TC、TG、LDL呈正相关（P＜0.001）。控制性别后,偏相关检验PBF与TC、TG、LDL仍呈正相关（P＜0.05）。结论:肿瘤患者血脂受多种因素影响,TC、TG、LDL与PA、PBF正相关,肿瘤患者应避免血脂过低。脂代谢调节治疗和抗肿瘤药物对于血脂异常的影响,有待进一步研究。     

双克隆型多发性骨髓瘤五例

目的观察双克隆型多发性骨髓瘤（MM）患者的临床特点及疗效。方法分析1996年1月至2010年6月收治的5例双克隆型MM患者，男性2例，女性3例，年龄59～76岁，中位年龄72岁。其中IgG＋IgA型3例，IgM＋IgG／A型2例。结果本组患者中诊断时均为DS分期Ⅲ期，4例治疗者中，2例达到部分缓解（PR），1例为稳定（SD），1例为进展（PD），无达到完全缓解（CR）的病例。结论双克隆型MM较为罕见，目前对此型MM的诊断和治疗尚缺乏更深刻的认识，需要更多病例的分析。     

环孢素A 抑制亲环素A 对多发性骨髓瘤细胞增殖的影响

  目的  亲环素A（cyclophilinA,CyPA）在多种肿瘤组织中高表达,在肿瘤形成发展中扮演重要的角色。本研究对CyPA在多发性骨髓瘤（multiple myeloma,MM）患者骨髓标本中的表达及其对MM细胞增殖、凋亡能力的影响进行研究,探讨其与MM发生、进展的相关性。  方法  采用ELISA法检测骨髓标本及细胞培养上清中CyPA水平。不同浓度环孢素A（cyclosporin A,CsA）刺激MM细胞,CCK-8法检测细胞增殖能力、Western blot法检测PARP蛋白裂解评价细胞凋亡水平。  结果  单克隆免疫球蛋白血症、冒烟型骨髓瘤、MM患者骨髓中CyPA浓度逐渐升高,至MM达最高值,患者治疗后CyPA浓度明显下降。CsA处理MM细胞后,CyPA分泌减少,随时间延长细胞增殖能力呈浓度依赖性逐渐减弱,PARP蛋白裂解增加、细胞凋亡增多。  结论  随MM恶性程度增加,骨髓中CyPA浓度显著升高,经治疗缓解后CyPA浓度显著下降,CyPA介导的细胞增殖在MM致癌机制中可能起关键作用。CsA作为CyPA作用的抑制剂,具有促进细胞凋亡、阻碍细胞增殖的作用,无免疫抑制作用的CsA衍生物可能是潜在的MM有效治疗手段。      

47例多发性骨髓瘤染色体分析及其临床意义

 目的　研究多发性骨髓瘤（MM）的细胞遗传学特征及其与临床预后的关系。方法　搜集47例临床病例并将患者的骨髓细胞进行了24 h短期培养,用常规方法制备染色体,R显带技术进行核型分析。结果　47例MM患者的异常检出率为14.9 % （7／47）。7例均有结构异常,包括易位、增加和丢失等,累及多种标记染色体等;发生于MMⅢ期6例,MMⅠ期1例; IgG 型2例,IgA型2例,IgD型1例,轻链型2 例。有异常核型的MM患者血红蛋白（Hb）、β2微球蛋白（β2-MG）、C反应蛋白（CRP）、乳酸脱氢酶（LDH）、原浆细胞比例均高,与无核型改变的MM比较,差异有统计学意义（P均＜0.05）。结论　MM的细胞遗传学多为复杂畸变,涉及多条染色体的数目和结构异常; 初诊或疾病进展时应做染色体检查等上述检查,以评估预后。     

毛细管电泳技术在多发性骨髓瘤诊断及MRD监测中的价值

目的:探讨毛细管电泳免疫分型技术在多发性骨髓瘤初诊及微小残留病变(MRD)监测中的意义.方法:采用毛细管电泳免疫分型技术对临床疑似由单克隆免疫球蛋白增多引起的肾病、血液病等初诊患者671例进行血清检测.连续追踪32例初诊诊断为多发性骨髓瘤的患者,毛细管分型电泳监测MRD,并与流式细胞仪监测结果进行对比.结果:单克隆免疫球蛋白增多者265例,阳性率39.5％,其中IgG-K型91例(34.3％),IgG-λ型57例(21.5％),lgA-K型25例(9.4％),IgA-λ型20例(7.5％),IgM-K型16例(6.0％),IgM-λ型5例(1.9％),游离K轻链型12例(4.5％),游离λ轻链型26例(9.8％),双克隆型11例(4.2％),其它型2例(0.8％).连续监测32例多发性骨髓瘤患者MRD,患者诱导化疗缓解后3个月毛细管电泳MRD监测阳性率为46.9％,流式细胞仪阳性率为75.0％,两种方法比较,差异有显著性(P＜0.05);诱导化疗缓解后6个月毛细管电泳MRD监测阳性率为28.1％,流式细胞仪阳性率为43.8％,两种方法比较无显著性差异.结论:毛细管电泳免疫分型技术对多发性骨髓瘤的诊断具有较高的敏感性及特异性,MRD监测虽不及流式细胞仪灵敏,但与流式细胞仪同时监测可减少漏检率.     

Antibodies contained in "M" component of some patients with multiple myeloma are directed to food antigens?

Multiple myeloma is malignant disease that is characterized in most patients, by the presence in the serum of monoclonal gamma globulins, which in agarose gel after electrophoresis appear as protein band of restricted mobility, “M” component.

The aim of this study was to determine are the antibodies contained in M-component directed to some antigen chronically present in the organism, to some of food antigens.

Seventeen patients with secretory plasmacytoma were included in the study: eight of them had IgG(kappa), three had IgG(lambda), and one had biclonal IgG(kappa) and IgA(kappa), while two had IgA(kappa), the other two IgA(lambda) and one IgM(lambda) as paraproteins. M-proteins were detected analyzing patients’ sera by agarose gel electrophoresis in 0.09 M barbital buffer. The each M-protein was confirmed by immunotyping (immunofixation) with corresponding antihuman antibodies directed to heavy or light chains of immunoglobulins. After the patients serum separation on agarose gel by electrophoresis, fresh 0.4% solution of crude gliadin (Sigma) in 1% SDS was put over the slides for immunoprecipitation.

Preliminary results showed the interaction of gliadin with patient's serum proteins present in the protein fraction of the same mobility as it was the mobility of the M-component, in 6 from 17 investigated sera.

These results are the first reporting that in sera of some patients with multiple myeloma antibodies from M-component could be directed to some of gliadin antigens.

As the serum antigliadin immunoreactivity is present in patients with gluten intolerance, celiac disease, it could be of importance to elucidate is the multiple myeloma more severe form of gluten intolerance than celiac disease.     

多发性骨髓瘤相关肾损害的危险因素

目的:分析多发性骨髓瘤相关肾损害的危险因素。方法:回顾性分析2009年1月-2013年12月我院收治的多发性骨髓瘤89例患者资料。将患者分为A组（肾功能正常）57例,B组（肾功能损害）32例,各因素首先采取单因素分析,对具有统计学意义的因素进一步采取非条件多因素Logistic回归分析。结果:单因素分析显示,两组患者Hgb、血Ca、血P、血URIC、血清β2-MG、尿本周氏蛋白、轻链类型、感染以及肾毒性药物九个因素比较,差异具有统计学意义（P＜0.05）。对上述单因素具有统计学意义的八个因素进行多因素Logistic回归分析,血Ca、轻链类型以及Hgb三个因素进入回归模型（P＜0.05）。结论:肾损害是多发性骨髓瘤患者的主要表现,高血钙、单克隆免疫球蛋白游离轻链类型以及贫血是多发性骨髓瘤患者发生相关性肾损害的独立危险因素。     

Serum lipids and lipoprotein disorders in cancer patients

Total serum cholesterol, free and esterified cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, serum triglycerides and serum lipoproteins were measured in 103 consecutive cancer patients (60 men and 43 women; mean age, 56 years) and 100 age-matched noncancer inpatients. Cancer patients as a group demonstrated significantly lower total cholesterol, esterified cholesterol and LDL cholesterol, compared with noncancer patients. Breast cancer proved to be an exception associated with increased serum total cholesterol, free cholesterol, LDL cholesterol, and triglycerides. a-lipoproteins were constantly increased in cancer patients whereas no differences were found in the other lipoprotein fractions. Finally, the observed overall incidence of hyperlipidemia in cancer patients (23/103) was not significantly different from the controls (29/100).     

Diagnostic criteria of multiple myeloma.

Immunoelectrophoresis or immunofixation is necessary for the identification of a monoclonal protein. During 1990 at the Mayo Clinic, 787 patients were found to have a monoclonal gammopathy. IgG accounted for 61% of the cases, followed by IgM (18%), IgA (11%), Bence Jones proteinemia (6%), biclonal gammopathy (3.5%), and IgD (0.5%). Monoclonal gammopathy of undetermined significance accounted for approximately two thirds of patients. This denotes the presence of a monoclonal protein in persons without evidence of multiple myeloma, macroglobulinemia, amyloidosis, or other related diseases. During long-term follow-up of patients with monoclonal gammopathy of undetermined significance, we found that one fourth developed multiple myeloma or related disorders. The interval from recognition of the monoclonal gammopathy to the diagnosis of multiple myeloma ranged from 2 to 29 years (median, 10 years). Waldenstr?m's macroglobulinemia developed in seven patients 4 to 20 years (median, 8.5 years) after recognition of the monoclonal protein. Systemic amyloidosis (AL) was found in eight patients 6 to 19 years (median, 9 years) after the diagnosis of a serum monoclonal protein. Five patients developed a malignant lymphoproliferative process 6 to 22 years (median, 10.5 years) after recognition of a monoclonal protein. Minimal criteria for the diagnosis of multiple myeloma include the presence of at least 10% abnormal plasma cells in the bone marrow or histologic proof of a plasmacytoma, the usual clinical features of multiple myeloma, and at least one of the following abnormalities: monoclonal serum protein (usually greater than 3 g/dL), monoclonal protein in the urine, or osteolytic lesions. No single technique differentiates benign from malignant plasma cell proliferation. The most dependable means is serial measurement of the monoclonal protein in the serum and urine and periodic reevaluation of pertinent clinical and laboratory features to determine whether multiple myeloma, systemic amyloidosis, macroglobulinemia, or other lymphoplasma cell proliferative disease has developed.     

Biclonal gammopathy in multiple myeloma: a case report

Monoclonal gammopathy is a group of B-cell disorders which result in the production of a specific and unique monoclonal immunoglobulin (M-component). Biclonal gammopathy is characterized by the simultaneous appearance of two different M-components. The incidence is about 1% of all monoclonal gammopathy. This paper reports on a 48-year-old male who had a chief complaint of back-pain beginning 7 months earlier. A physical examination was unremarkable, except for anemia and tenderness in the back. Hemoglobin was 5.4 g/dl, white blood cells 4.5 x 10(3)/microliter, platelets 157 x 10(3)/microliter, and reticulocytes 0.9%. Serum iron was 79 mg/dl, and total iron-binding capacity was 210 mg/dl. A blood smear showed the formation of rouleaux, but no plasma cells were found. Serum creatinine was 5.4 mg/dl, with a creatinine clearance of 18.1 ml/min. Serum electrolytes were normal except for serum calcium which was 14.4 mg/dl. The urinalysis showed strongly positive proteinuria (+2), with negative Bence Jones protein. Serum protein electrophoresis showed an increase and a spike pattern of beta-2 globulin (2.8 g/dl) and alpha-2 globulin (1.5 g/dl), with normal gamma globulin. By nephelometry technique, serum IgG was normal (1388 mg/dl), IgA was high (900 mg/dl), and IgM was also high (517 mg/dl). Advanced and extensive osteolytic lesions were found in the clavicle, ribs, skull, humerus, femur, and columna vertebralis. Plasma cells (myeloma cells) in bone marrow were 32%. The clinical diagnosis was multiple myeloma (biclonal gammopathy) stage IIIB (Durie and Salmon staging system). Clinical response was good after two series of conventional chemotherapy, with normal serum electrophoresis, decreasing serum creatinine and serum calcium. Based on the above data, the diagnosis of multiple myeloma with biclonal gammopathy was confirmed. This is a rare case with a combination of IgA and IgM M-components.     

Serologic prevalence of antibody to human herpesvirus type 8 in patients with various monoclonal gammopathies

Both viral and serologic studies have consistently shown an association of human herpesvirus type 8 (HHV-8) with Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease. The presence of HHV-8 DNA in patients with myeloma has been reported by some investigators but not substantiated by others. In addition, variable results have been obtained with serologic studies for HHV-8 in patients with myeloma and certain other monoclonal gammopathies (MG). We tested 238 coded serum or plasma samples from 96 patients with various MG for antibodies to lytic and latent HHV-8 antigens by indirect immunofluorescence. Thirty-four of 96 (35%) patients were positive for the lytic antibody, but none were positive for the latent antibody. Patients with kappa or lambda light chain myeloma were often positive for the lytic antibody when compared to patients with IgG or IgA myeloma (8 of 11 [73%] vs. 12 of 38 [32%], P = 0.033). The patients with light chain myeloma also were more likely to be positive when compared to patients with Waldenstr?m's macroglobulinemia (WM) (4 of 15 [27%], P = 0.045) or AL amyloidosis (4 of 13 [31%], P = 0.047). Four of 9 (44%) patients with monoclonal gammopathy of undetermined significance (MGUS) were positive. However, 4 other patients who progressed from MGUS to myeloma were negative. Subgroup analysis of MG may help clarify the role of HHV-8 in these disorders.     

Smoldering Multiple Myeloma: Emerging Concepts and Therapeutics

Smoldering multiple myeloma (SMM) is a pre-malignant condition with an inherent risk for progression to multiple myeloma (MM). The 2014 IMWG guidelines define smoldering multiple myeloma as a monoclonal gammopathy disorder with serum monoclonal protein (IgG or IgA) ≥30 g/L or urinary monoclonal protein ≥500 mg per 24 h and/or clonal bone marrow plasma cells 10–60 % without any myeloma-defining events or amyloidosis. The risk for progression of SMM to MM vary based on clinical, laboratory, imaging, and molecular characteristics. Observation, with periodic monitoring is the current standard of care for SMM. Over last few years, research advances in SMM have led to the delineation of newer risk factors for progression and identification of a “high-risk” group that would potentially benefit from early treatment. This review focuses on advances in the SMM risk-stratification model and recent clinical trials in this patient population.