多发性骨髓瘤双侧乳腺浸润1例

多发性骨髓瘤（multiple myeloma,MM）是浆细胞异常增生恶性肿瘤,是一种进行性的肿瘤性疾病,其特征为骨髓浆细胞瘤和一株完整性的单克隆免疫球蛋白（IgG,IgA,IgD或IgE）或Bence Jones蛋白质（游离的单克隆性κ或γ轻链）过度增生。     

新型免疫调节剂泊马度胺抗肿瘤治疗临床转化的现状

泊马度胺（pomalidomide）为高效的第三代免疫调节剂（immunomodulatory drug,IMiD）,其药理机制类似第一代IMiD沙利度胺,但较后者具有更强的体内外抗血管新生、抗肿瘤、抗炎症及抗骨髓瘤作用,且不良反应相对较少,患者口服耐受性良好。2013年2月,泊马度胺已获美国FDA批准用于复发/难治多发性骨髓瘤（multiple myeloma,MM）患者。本文重点就泊马度胺治疗复发/难治MM、骨髓纤维化、免疫球蛋白轻链型淀粉样变性（immunoglobulin light-chain amyloidosis,AL）、小细胞肺癌及其他晚期实体肿瘤的临床转化现状作一讨论。     

IgD型多发性骨髓瘤的诊治现状及展望

IgD型多发性骨髓瘤（IgD multiple myeloma，IgD MM）是多发性骨髓瘤（multiple myeloma，MM）中一种罕见类型，以年轻男性患者居多。主要表现为高钙血症、肾衰竭、贫血、骨损害、髓外浸润和系统性淀粉样变性等，具有侵袭性高，预后较差的特点。近年来，随着免疫调节剂（沙利度胺、来那度胺）、蛋白酶抑制剂（硼替佐米）等药物以及自体造血干细胞移植（autologous stem cell transplantation，ASCT）的应用，IgD型MM的预后得到明显改善。新一代蛋白酶体抑制剂、CD38单克隆抗体、组蛋白去乙酰化酶抑制剂（histone deacetylase inhibitor,HDACI）、新型免疫治疗技术等治疗方法也为IgD型MM 的治疗提供了新的方向。目前关于IgD型MM的相关报道较少，本文就IgD型MM的临床特点、诊断、治疗、预后及新药研究现状进行如下综述。     

多发性骨髓瘤的诊断进展与分期

多发性骨髓瘤(multiple myeloma,MM)是一种浆细胞恶性肿瘤,随着研究的深入,对MM的诊断不再局限于骨髓活检与影像学检查,而是向血清游离轻链、细胞遗传学和分子生物学检测方向发展,这使医务人员对该疾病的发生机制有了更深的了解,同时为预后评估提供了重要依据。下面主要从MM的实验室检查、诊断标准和分期3个方面对近年MM的诊断及其进展进行综述。     

多发性骨髓瘤患者外周血miR-21的表达与意义

目的：检测多发性骨髓瘤（multiple myeloma,MM）患者外周血miR-21表达水平,探讨miR-21在MM发生、发展中的调控作用及临床意义.方法：选择30例MM患者、15例MGUS患者及20例正常对照的,测定其血清β2-MG、IgA、IgM、IgG、λ、κ、TP、ALB、Hb、LDH及Ca2＋等水平含量.用SYBR Green实时荧光定量PCR检测miR-21表达水平.相关检验分析MM患者外周血miR-21水平与临床指标相关性.结果：MM组血清循环miR-21的表达水平较MGUS组和NC组显著增高,差异有统计学意义（P＜0.01）.根据ISS分期,MM组中Ⅰ期miR-21、IgG、κ及ALB水平较Ⅱ期和Ⅲ期明显降低或增高,Ⅲ期IgA、β2-MG和λ的水平较Ⅰ期和Ⅱ期显著增高,差异均有统计学意义（P＜0.05或P＜0.01）.MM患者miR-21水平与κ、（κ＋λ）、IgG、（IgG＋ IgA＋ IgM）和β2-MG呈正相关,与ALB呈负相关（均P＜0.01）.结论：miR-21过表达在MM的发病中发挥着重要的致癌基因作用,miR-21与MM的发生发展和疾病预后有密切关系,可作为判断MM患者预后不良指标之一.     

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。     

颅脑为首发症状累及蝶窦的IgDλ型多发性骨髓瘤1例报道

<正>多发性骨髓瘤（multiple myeloma,MM）是指骨髓中浆细胞发生单克隆增生并分泌M蛋白，是一种血液系统恶性肿瘤。IgD型的多发性骨髓瘤较为少见。多发性骨髓瘤较少发生髓外浸润，而发生在蝶窦区的髓外浸润则更为罕见。发生在蝶窦区的多发性骨髓瘤在临床症状和影像学表现上缺乏特异性，     

患者报告结局与多发性骨髓瘤的研究进展

在疾病诊疗过程中,获得患者对疾病经历的看法非常重要。患者报告结局（patient-reported outcomes,PROs是用于获取患者观点的标准化措施,直接来自患者,无需临床医师解释,主要通过描述患者对疾病、治疗及医疗保健系统作用的评估,从而提供对病情、疾病影响及功能影响的感知。PROs提供了其他来源无法获得的信息,其价值越来越得到临床、护理及参与卫生服务管理者的认可。本文结合目前国内外的PROs研究进展,综述其在多发性骨髓瘤（multiple myeloma,MM）中的应用,旨在更好地指导MM患者的综合管理。     

初诊老年多发性骨髓瘤患者研究进展：第19届欧洲血液学会年会报道

随着新的靶向骨髓瘤药物的应用,初诊老年多发性骨髓瘤（multiple myeloma,MM）患者的中位生存期从30个月延长至60个月,但具有一些高危预后因素的老年患者临床结果仍欠佳.文章结合第19届欧洲血液学会年会相关报道,从标准治疗方案、治疗方式、预后因素三个方面对初诊老年MM患者的研究进展作一介绍.     

微小残留病检测在多发性骨髓瘤移植后患者中的应用现状与思考

多发性骨髓瘤（multiple myeloma,MM）患者的治疗疗效在近十年来不断提高,特别是在新药联合移植治疗后,其无进展生存期（progression free survival,PFS）和总生存期（overall survival,OS）均大幅延长。对于患者的疗效而言,传统意义的评效标准完全缓解（complete response,CR）已经不能满足其对预后的指导,微小残留病（minimal residual disease,MRD）的评估应运而生,其检测方法发展较快。血清游离轻链（serum free light chain,sFLC）、流式细胞术、聚合酶链式反应（polymerase chain reaction,PCR）、二代测序（next-generation sequencing,NGS）和PET-CT等各项技术层出不穷。本文就上述各检测手段在MM移植后患者中的应用现状予以综述。      

Monoclonal Gammopathies After Renal Transplantation: A Single-center Study

IntroductionPlasma cell disorders (PCDs) are clonal plasma cell disorders that include conditions such as monoclonal gammopathy of undetermined significance (MGUS), monoclonal gammopathy of renal significance (MGRS), multiple myeloma (MM), smoldering MM (SMM), solitary plasmacytoma, and light-chain (AL) amyloidosis. The risk factors associated with and the clinical course of PCDs after renal transplantation is not well established although immunosuppressive protocols may impact the incidence and natural history of PCDs posttransplant.Patients and MethodsThis single-center retrospective study evaluated patients with a history of renal transplant who developed a PCD between January 1, 2014-December 31, 2018.ResultA total of 41 patients met the inclusion criteria including 29 with MGUS and 12 with symptomatic PCD (4 with MM, 2 with SMM, 4 with MGRS, 1 with AL amyloidosis, and 1 with solitary plasmacytoma). The median follow-up of survivors was 41.6 months. Three patients (1 with MGUS and 2 with MGRS) progressed to MM during the follow-up period. There was a male preponderance in both groups. There was no correlation between the donor and immunosuppressive regimen and the development of a PCD. Patients with symptomatic PCD had higher serum creatinine and M-protein levels at diagnosis and higher free light chain ratio and plasma cell burden. There was also a higher percentage of allograft failure noted in the symptomatic PCD subset 50% (n = 6), whereas only 23% (n = 7) of patients had allograft failure in the MGUS group.ConclusionThis study shows the importance of considering monoclonal gammopathy in the differential of renal dysfunction after kidney transplant and the need to follow these patients closely to monitor for progression to symptomatic PCD.     

Understanding biology to tackle the disease: Multiple myeloma from bench to bedside,and back

Answer questions and earn CME/CNE Multiple myeloma (MM) is a cancer of antibody‐producing plasma cells. The pathognomonic laboratory finding is a monoclonal immunoglobulin or free light chain in the serum and/or urine in association with bone marrow infiltration by malignant plasma cells. MM develops from a premalignant condition, monoclonal gammopathy of undetermined significance (MGUS), often via an intermediate stage termed smoldering multiple myeloma (SMM), which differs from active myeloma by the absence of disease‐related end‐organ damage. Unlike MGUS and SMM, active MM requires therapy. Over the past 6 decades, major advancements in the care of MM patients have occurred, in particular, the introduction of novel agents (ie, proteasome inhibitors, immunomodulatory agents) and the implementation of hematopoietic stem cell transplantation in suitable candidates. The effectiveness and good tolerability of novel agents allowed for their combined use in induction, consolidation, and maintenance therapy, resulting in deeper and more sustained clinical response and extended progression‐free and overall survival. Previously a rapidly lethal cancer with few therapeutic options, MM is the hematologic cancer with the most novel US Food and Drug Administration‐approved drugs in the past 15 years. These advances have resulted in more frequent long‐term remissions, transforming MM into a chronic illness for many patients. CA Cancer J Clin 2014;64:422–444. © 2014 American Cancer Society.     

Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021

Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.Subject terms: Myeloma, Chemotherapy     

Polyclonal serum IgM level identifies a subgroup of multiple myeloma patients with low-risk clinicobiological features and superior survival

Normal plasma cells (PCs) are either undetectable or outnumbered by the myelomatous PC compartment in bone marrow of multiple myeloma (MM). However, residual normal PCs have been detected in a minority of symptomatic MM patients with superior survival. The number of normal PCs is also an important factor to identify monoclonal gammopathy of undetermined significance (MGUS)-like MM. We speculate that the polyclonal serum IgM level in non-IgM myelomas may reflect the number of residual normal PCs. Here we investigated the prognostic relevance of polyclonal serum IgM level in a series of 485 newly diagnosed symptomatic MM (NDMM) patients. Our results showed that symptomatic MM patients with polyclonal IgM more than 0.5 g/L displayed a favorable baseline clinical feature, together with a significantly lower frequency of high-risk cytogenetic abnormalities. This group of patients had a significantly prolonged progression-free survival (PFS) and overall survival (OS) regardless of thalidomide or bortezomib therapy. Furthermore, the superior outcome was independent of the depth of response. Our findings suggest that polyclonal IgM level is capable of identifying a group of symptomatic MM patients with distinct clinicobiological characteristics and favorable survival, similar with MGUS-like MM.     

The Value of the Bone Marrow Plasma Cell Cytoplasmic Light Chain Ratio in Differentiating Between Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

We compared the plasma cell light chain ratios in the bone marrows of 13 patients with multiple myeloma (MM), with those of 13 patients with monoclonal gammopathy of undetermined significance (MGUS). The mean light chain ratio in favour of the paraprotein isotype in the myeloma group was 51.83 (95% confidence limits (CL) 29.52-74.14) while in the MGUS group it was 5.30 (CL 2.07-8.52). The difference between the MGUS and MM groups was significant (p = 0.0005). Neither the bone marrow plasma cell count nor the paraprotein level were significantly correlated with the light chain ratio in either of these two groups. We found a cut-off ratio of 8 to be the most useful in differentiating between myeloma and MGUS. Only one patient with myeloma had a ratio below 8, and one MGUS patient had a ratio above this cut-off point. We conclude that determination of the bone marrow plasma cell light chain ratio is a simple and useful test in differentiating between myeloma and MGUS in difficult cases.     

Analysis of chromosome 12p deletion in plasma cell dyscrasias

The prognostic relevance of 12p deletion is controversial in multiple myeloma (MM) and the status of 12p deletion is unknown in other plasma cell disorders. We investigated 12p deletion in 88 patients with MM, 19 patients with monoclonal gammopathy of undetermined significance (MGUS), and 17 patients with plasma cell leukemia (PCL). Cytoplasmic immunoglobulin light chain immunofluorescence with simultaneous FISH analysis (cIg-FISH) detected hemizygous 12p deletion in 8% of MM and 24% of PCL, respectively, but in none of the MGUS cases (p = 0.0366). 12p deletions were found in 5 of 7 (71%) MM patients at diagnosis with stage III disease (Durie-Salmon), 2 of 7 (28%) with stage I or II. Of 11 cases with 12p deletions, 6 (55%) had coexistence of p53 deletions, including 3 of 7 (42%) MM, and 3 of 4 (75%) PCL cases. There were no significant differences in progression free or overall survivals in MM patients with or without 12p deletions. Our results do not support the use of 12p deletion as a prognostic marker in MM, rather, it tends to occur in advanced disease, may represent a secondary change associated with the disease progression.     

Hyperdiploidy is a common finding in monoclonal gammopathy of undetermined significance and monosomy 13 is restricted to these hyperdiploid patients.

PURPOSE: Two pathways, hyperdiploid and nonhyperdiploid, are proposed for progression to plasma cell neoplasia. Implication of monosomy 13 (Delta13) is unclear in monoclonal gammopathy of undetermined significance (MGUS), and data on DNA content of plasma cells [DNA index (DI)] are rare. EXPERIMENTAL DESIGN: We ascertained DI in 169 multiple myeloma (MM) and 96 MGUS patients. Interphase fluorescence in situ hybridization (FISH) coupled to cytoplasmic staining of specific Ig (cIg-FISH) was done to look for trisomies and to ascertain Delta13. RESULTS: Hyperdiploidy and hypodiploidy were found in 54% and 11.5% of MGUS patients and in 59.5% and 25% of MM patients, respectively. In MGUS patients tested using probes for odd chromosomes, cIg-FISH showed association between trisomies for chromosomes 3, 7, 9, 11, or 15 and hyperdiploidy. Delta13 was found in 45.3% and 24.6% of MM and MGUS patients, respectively. Most Delta13 cases observed in MGUS were found within hyperdiploid clones, 38% versus 11% in hypodiploid cases, in sharp contrast with the occurrence of Delta13 in MM patients, 31.9% and 76.3%, respectively. That peculiar distribution of Delta13 according to DI persisted with other thresholds used to ascertain hyperdiploidy, such as DI >or= 1.05. A strong relationship between IgA peak and hypodiploidy (P = 0.007) was only observed in MM, whereas lambda light chain was significantly associated with hypodiploidy in MGUS (P = 0.001) and MM (P = 0.05). Hyperdiploidy shows similar pattern in MGUS and MM. CONCLUSION: This fits well a hyperdiploid pathway leading to MM after a preceding MGUS stage. Yet-to-be-determined secondary event(s) needs to occur for the transition to MM, unrelated to changes in chromosome number or to loss of chromosome 13. In contrast, the "nonhyperdiploid" pathway needs to be clarified further because hypodiploidy is less common in MGUS than in MM and Delta13 is rare in hypodiploid MGUS patients compared with hypodiploid MM patients.     

The Immunotyping Distribution of Serum Monoclonal Paraprotein and Environmental Impact on Multiple Myeloma (MM) and Monoclonal Gammopathy of Uncertain Significance (MGUS) in Taiwan: A Medical Center-Based Experience

Background: Whether ambient exposure to environmental pollutants leads to hematopoietic malignancies such as multiple myeloma (MM) remains to be ascertained. Therefore, we aimed to investigate the immunotyping distribution of serum monoclonal paraprotein and the environmental influence on MM and monoclonal gammopathy of uncertain significance (MGUS) in the Taiwanese population. Materials and Methods: Serum protein electrophoresis with immunosubtraction by the capillary zone electrophoresis method was performed as primary screening for MM and MGUS. Clinical, pathological, and residence data of patients were also obtained. Results: From August, 2013 to June, 2015, a total of 327 patients underwent serum protein electrophoresis with immunosubtraction. Among these, 281 demonstrated no remarkable findings or non-malignant oligoclonal gammopathy, 23 were detected to have MGUS, 18 were identified as MM, and a further 5 were found as other malignancies. The most frequent immunotyping distribution of serum monoclonal paraprotein was IgG kappa (54.3%, n=25), followed by IgA lambda (15.2%, n=7) and IgG lambda (10.9%, n=5) in subjects with gammopathy. Additionally, it was shown that the elderly (OR: 4.61, 95% CI: 1.88-11.30, P<0.01) and males (OR: 2.04, 95% CI: 1.04-4.02, P=0.04) had significantly higher risk of developing MM and MGUS. There was no obvious impact of environmental factors on the health risk of MM and MGUS evolution (OR: 0.77, 95% CI: 0.40-1.50, P=0.49). Conclusions: The most frequent immunotyping distribution of serum monoclonal paraprotein included IgG kappa, IgA lambda and IgG lambda in MM and MGUS in the Taiwanese population. The elderly and male subjects are at significantly higher risk of MM and MGUS development, but there was no obvious impact of environmental factors on risk.     

Over one‐third of African‐American MGUS and multiple myeloma patients are carriers of hyperphosphorylated paratarg‐7, an autosomal dominantly inherited risk factor for MGUS/MM

As hyperphosphorylated paratarg‐7 (pP‐7) carrier state was shown to be the first molecularly defined autosomal dominantly inherited risk factor for monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) in a European population, the prevalence of pP‐7 carrier state among African‐Americans who have a significantly higher incidence of MGUS/MM is of interest. We therefore determined pP‐7 carrier state and paraproteins with specificity for P‐7 in African‐American, European and Japanese patients with MGUS/MM and healthy controls. By isoelectric focusing and ELISA, a paratarg‐7‐specific paraprotein and the associated pP‐7 carrier state was observed in 30/81 (37.0%) African‐American, 42/252 (16.7%) European and 7/176 (4.0%) Japanese MGUS/MM patients (p < 0.001). A pP‐7 carrier state was found in 11/100 (11.0%) African‐American, 8/550 (1.5%) European and 1/278 (0.4%) Japanese healthy controls (p < 0.001), resulting in an odds ratio for MGUS/MM of 4.8 (p < 0.001) among African‐American, 13.6 among European (p < 0.001) and 11.5 (p = 0.023) among Japanese carriers of pP‐7. We conclude that pP‐7 carriers are most prevalent among African‐Americans, but a pP‐7 carrier state is the strongest molecularly defined single risk factor for MGUS/MM known to date in all three ethnic groups. The high prevalence of pP‐7 carriers among African‐American patients emphasizes a predominant role of this genetic factor in the pathogenesis of these diseases. The large number of pP7 African‐American patients and controls should facilitate the identification of the SNP or mutation underlying the pP‐7 carrier state.     

C-Myc在多发性骨髓瘤中的研究进展

多发性骨髓瘤(multiple myeloma,MM)是一种浆细胞恶性增殖性疾病,其特点为克隆性浆细胞在骨髓中异常增殖,发病率在血液系统肿瘤中排第2位.C-Myc是一种原癌基因,在人类的多种实体肿瘤和血液肿瘤中异常高表达.近年来相关研究表明,C-Myc的表达增强与肿瘤的不良预后息息相关.从癌前病变单克隆丙种球蛋白病(m...