累及中枢神经系统多发性骨髓瘤9例

目的:探讨多发性骨髓瘤累及中枢神经系统的诊治及其预后.方法:回顾性分析9例累及中枢神经系统的多发性骨髓瘤患者的诊治及其预后.结果:418例多发性骨髓瘤患者中有9例并发中枢神经系统侵犯,发生率为2.2%,其中脑膜受累最为常见(5/9),其次为垂体(2/9).所有患者在诊治过程中均伴有多处其他部位软组织的髓外病变.中位随访时间为30个月,9例患者的中位生存时间为29个月,累及中枢神经系统后中位生存时间仅为5个月.结论:多发性骨髓瘤累及中枢神经系统较为少见,受累部位以脑膜最为常见,常合并其他部位的软组织浆细胞瘤.累及中枢神经系统的多发性骨髓瘤患者预后不良,在治疗上尚缺乏有效的干预手段.     

放疗对初诊时伴髓外病变的多发性骨髓瘤患者的疗效分析

  目的  分析放疗对初诊时伴髓外病变的多发性骨髓瘤（MM）患者的疗效及对预后的影响。  方法  回顾性分析本院自2000年1月至2012年8月收治的52例初诊时伴有髓外病变的多发性骨髓瘤患者的临床特点及其预后相关因素，分析放疗疗效及对预后的影响。  结果  52例患者中位年龄60（31~81）岁，髓外病变最多见于软组织（69.2%）。其中13例患者接受放疗，中位放疗剂量45 Gy。患者预计总生存（OS）时间为42.5个月。而接受放疗与否对患者总缓解率及预后差异均无统计学意义（P > 0.05）。单因素分析显示Hb≤110 g/L（P=0.009）、β2-MG≥5.5（P=0.049）为该类患者预后不良指标；Cox多因素分析显示，仅β2-MG为本组患者的独立预后因素（P=0.014）。  结论  放疗不能改善初诊时伴髓外病变的MM患者的预后，可能需要联合硼替佐米等新药或进行自体造血干细胞移植来改善预后。      

多发性骨髓瘤伴髓外病变研究进展

多发性骨髓瘤（MM）是一种以分泌单克隆免疫球蛋白或其片段（M蛋白）为特征的恶性浆细胞疾病。一般情况下,骨髓瘤细胞局限于髓内,但在初诊或疾病进展过程中均可出现髓外病变（EM）,伴EM的MM患者预后较差。根据EM的发生方式可将其分为单纯骨相关髓外病变（EM-b）和软组织相关髓外病变（EM—s）。EM—b为骨髓瘤细胞突破骨皮质累及周围连续性软组织的病变;EM-s为通过血源播散到髓外的软组织或其他器官的病变。研究发现不论是初诊MM还是疾病进展过程中发生的EM-s,其预后都比EM-b差。因此,文章主要综述EM-b和EM-S的区别,包括两者的发病率、生物学特征、临床表现、治疗及预后。     

多发性骨髓瘤继发急性髓系白血病自发缓解一例并文献复习

目的观察多发性骨髓瘤继发急性髓系白血病出现自发缓解的影响因素、病理变化、自然病程,以探究多发性骨髓瘤病情变化过程中的诊查治疗思路。方法回顾性分析上海中医药大学附属龙华医院收治的1例多发性骨髓瘤继发急性髓系白血病患者的临床资料,并复习相关文献。结果该例患者确诊多发性骨髓瘤后行BCD方案诱导化疗,病程中出现继发急性髓系白血病,暂缓治疗1个月后,复查血象、骨髓象提示急性髓系白血病自发缓解,约4个月后患者急性白血病复发,最终死亡。结论多发性骨髓瘤治疗过程中出现继发急性髓系白血病的案例并不少见,且多提示病情变化,预后不良。本例患者虽罕见地出现了继发白血病的自发缓解,但无进展生存时间短,相关个体化诊治方案需进一步探索。     

多发性骨髓瘤髓外病变的临床特征分析

目的:探讨多发性骨髓瘤髓外病变（extramedullary disease,EMD）的临床分子学特征及预后因素。方法:共纳入67例多发性骨髓瘤髓外病变患者和97例多发性骨髓瘤非髓外病变患者。EMD再分为两组:第一组是由溶骨性病变直接延伸的肿瘤(EM-B),而第二组则是骨髓瘤细胞浸润软组织(EM-S)。两组间的计数资料采用卡方检验,计量资料符合正态分布采用t检验,不符合正态分布使用秩和检验来检测治疗结果的差异。绘制Kaplan-Meier曲线分析整个队列的总生存(OS),采用log-rank检验比较生存曲线。结果:EMD组血清铁蛋白（serum ferritin,SF）(P=0.035)、乳酸脱氢酶(lactate dehydrogenase,LDH)(P=0.043)的表达水平明显高于非EMD组。EM-S组诊断时发生t(4;14)细胞遗传学的比例高于EM-B组(P=0.034)。与EM-B组相比, EM-S组多部位发病概率较高。流式细胞学发现EMD组异常循环浆细胞（abnormal circulating plasma cells,aCPCs）的比例明显高于非EMD组（P=0.031）,病理标本显示髓外病变组活检组织中Ki-67增殖指数明显高于骨髓（P=0.019）。Kaplan-Meier曲线显示,非EMD组患者的OS明显高于EMD组(P=0.012)。而EM-S提示更短的OS。结论:部分临床指标（SF、LDH）及分子学特征(aCPCs)可作为EMD发生可能的预警因素。t(4;14)细胞遗传学异常和高的SF水平可能和EM-S发病有关。EMD患者总体OS比非EMD者差,进一步分析得出EM-S预后差于EM-B患者。常规化疗不能用于改善EMD患者预后和克服疾病本身的恶性程度,新的临床实验必须开展以探索EMD治疗标准、有效的化疗方案。     

骨的孤立性浆细胞瘤和髓外浆细胞瘤

在浆细胞病中，孤立性浆细胞瘤（骨的孤立性浆细胞瘤和髓外浆细胞瘤）比多发性骨髓瘤罕见，然而两者间关系仍不清楚。１９６０～１９９４年间，作者治疗骨的孤立性浆细胞瘤２４例，髓外浆细胞瘤２０例。诊断标准为：（１）临床与放射学检查未发现另外病变；（２）活检证实为浆细胞瘤；（３）骨髓检查阴性（浆细胞＜１０％）；（４）无贫血、高血钙或肾受累证据。随访平均１１２个月，骨的孤立性浆细胞瘤中５４％、髓外浆细胞瘤中４０％发展为多发性骨髓瘤，两者差异无显著意义（Ｐ＞０．０５）。作者建议将孤立性浆细胞瘤分为潜伏型与侵袭型：肿瘤细胞分化良好者病变趋向潜伏静止，低分化者病变具侵袭性，容易发展为多发性骨髓瘤。治疗选择广泛切除或彻底刮除，瘤腔用液氮或酚等灭活后植骨或骨水泥充填，术后辅以放疗。侵袭型者需辅以化疗，以延缓播散为多发性骨髓瘤。     

多发性骨髓瘤伴髓外病变患者硼替佐米方案治疗效果及生存分析

目的探讨新药时代伴髓外病变(EMD)多发性骨髓瘤患者的近期治疗效果及长期生存情况。方法回顾性分析2015年1月至2020年1月安徽皖北煤电集团总医院诊治的74例多发性骨髓瘤患者资料,其中伴软组织髓外病变(EM-S)患者17例,伴骨旁髓外病变(EM-B)患者9例,无髓外病变(No-EMD)患者48例。分析三组患者接受含硼替佐米方案治疗后的近期疗效、4年无进展生存(PFS)率和总生存(OS)率及其影响因素。结果早期硼替佐米方案诱导治疗3~4个疗程后,EM-S组总体反应率低于No-EMD组和EM-B组[58.8%(10/17)比85.4%(41/48)、100.0%(9/9)],差异均有统计学意义(χ2=13.7,P=0.036;χ2=26.5,P=0.003),而No-EMD组和EM-B组差异无统计学意义(χ2=12.7,P=0.211)。生存分析结果显示,No-EMD组4年PFS率高于EM-S组和EM-B组(41.0%比7.6%、0),差异均有统计学意义(χ2=10.835,P<0.01;χ2=8.276,P=0.004);EM-S组4年OS率低于No-EMD组和EM-B组(16.5%比54.3%、59.3%),差异均有统计学意义(χ2=9.146,P=0.002;χ2=4.066,P=0.044)。结论伴EM-S的多发性骨髓瘤患者硼替佐米方案早期治疗效果、PFS和OS均较差,而EM-B对OS无影响。     

14例髓外浆细胞瘤患者的临床特征分析及治疗

  目的   探讨伴髓外浆细胞瘤（extramedullary plasmacytoma,EMP）的多发性骨髓瘤（multiple myeloma,MM）患者的临床特点,治疗选择及预后。   方法   对14例确诊的伴髓外浆细胞瘤的多发性骨髓瘤进行回顾性分析。   结果   14例患者男女比为1:l,中位年龄56.9岁。9例患者初诊时即出现EMP,5例在治疗过程中发生。治疗选择包括化疗,手术,放疗或自体移植。6例患者单发EMP,8例多发EMP（multiextramedullary plasmacytomas,MEP）;单发患者中5例部分或接近完全缓解,1例病情进展;多发患者中5例死亡,1例病情进展,2例部分缓解。   结论   MM伴有MEP者对常规化疗反应差,预后不良,需要探讨新的治疗策略。      

伴有骨骼以外髓外浆细胞瘤的多发性骨髓瘤九例并文献复习

目的总结伴有骨骼以外髓外浆细胞瘤的多发性骨髓瘤（MM）患者临床表现及其治疗反应,加深对该病的认识。方法对2001年1月至2007年6月初诊或病情进展过程中出现骨骼以外髓外浆细胞瘤的9例患者临床表现及治疗反应进行分析。根据欧洲骨髓移植疗效标准对患者的治疗反应进行判断。结果9例患者中位年龄55（48～66）岁,男女比为8：1。1例患者在初诊时即出现骨骼以外髓外浆细胞瘤,8例患者在病情进展时出现：患者通常多个部位受累,对常规化疗反应差。中位随访19（3～47）个月,8例患者从病情进展到出现骨骼以外髓外浆细胞瘤的中位时间为4．5个月。而7例患者从出现骨骼以外髓外浆细胞瘤到死亡的时间为2个月,中位OS为23个月。结论伴有骨骼以外髓外浆细胞瘤的MM较罕见。患者通常多部位受累,对常规化疗反应差,预后不良。需要探讨新的治疗策略。     

25例多发性骨髓瘤的诊治分析

目的提高多发性骨髓瘤的诊治水平和生存质量.方法分析25例多发性骨髓瘤的临床特点、诊断、治疗及预后.结果25例多发性骨髓瘤经手术及骨髓穿刺确诊,随访时间2月至4年不等,失访按死亡计.生存期2月至44月,总体中位生存期20个月,Ⅱ期6例30个月,Ⅲ期19例17个月(P＜0.05).化疗16例,中位生存期20个月,手术加化疗7例,中位生存期22个月,(P＞0.05).加干扰素治疗12例,中位生存期28个月,不加干扰素中位生存期15个月(P＜0.05).加双磷酸盐10例,中位生存期22个月,不加双磷酸盐中位生存期16个月(P＞0.05),但骨痛缓解明显.结论提高多发性骨髓瘤的早期诊断率,以化疗为主的治疗,并应用干扰素及双磷酸盐,有助于提高生存质量,延长生存期、缓解期.     

Clinical analysis of 36 multiple myeloma patients with extramedullary plasmacytoma invasion of the spinal canal

Few physicians are familiar with extramedullary plasmacytoma (EMP) invasion of the spinal canal in multiple myeloma (MM) patients, and little information about this rare disease is available. The purpose of the present study was to investigate the clinical features, prognosis and treatment of MM patients with EMP invasion of the spinal canal. We evaluated 36 MM patients with EMP invasion of the spinal canal. EMP invasion was confirmed by magnetic resonance imaging, computed tomography and/or histopathological analysis of bone marrow biopsy samples. Patients underwent surgery followed by chemotherapy or received chemotherapy alone. Chemotherapy consisted of bortezomib‐containing regimens and other combination therapies. The patients' median age was 58.6 years (range, 31–78 years). Eight patients had negative immunofixation electrophoresis results, and nine patients had a bone marrow plasma cell infiltration rate of less than 5%. Of the 36 MM patients with EMP invasion of the spinal canal that we identified, 19 had thoracic spinal cord involvement, 10 had lumbar spinal cord involvement, 2 had sacral spinal cord involvement and 5 had both lumbar and thoracic spinal cord involvement. The findings of our study, which is the largest study in MM patients with EMP spinal canal invasion conducted to date, suggest the importance of the early detection of spinal invasion in MM patients. Extramedullary disease was resistant to conventional treatments but responded well to regimens containing novel drugs such as bortezomib. In patients with symptoms of nerve root involvement, the tumour should be resected as soon as possible to relieve spinal cord compression. Copyright © 2014 John Wiley & Sons, Ltd.     

Extramedullary Progression Despite a Good Response in the Bone Marrow in Patients Treated with Thalidomide for Multiple Myeloma

We report two patients who were treated with thalidomide for resistant multiple myeloma (MM) and developed extramedullary plasmacytomas despite a good response in the bone marrow. The first patient had progressive disease 18 months post autologous peripheral stem cell transplant. Two and a half months after the initiation of thalidomide therapy extensive new plasmacytomas of the skin and nasal mucosa appeared while the medullary response continued. The second patient was treated with thalidomide for resistant MM. Despite a medullary response he developed neurological signs compatible with cranial nerve involvement and an MRI study was suggestive of a plasmacytoma involving the sellar region.

We assume that a change in the expression of some adhesion molecules on the myeloma and/or the stromal cells is responsible for this phenomenon. Treating Physicians should be aware of this phenomenon in MM patients receiving thalidomide.     

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。     

Role of platelet-derived growth factor-AB in tumour growth and angiogenesis in relation with other angiogenic cytokines in multiple myeloma

Angiogenesis is a complex process essential for the growth, invasion, and metastasis of various malignant tumours, including multiple myeloma (MM). Various angiogenic cytokines have been implicated in the angiogenic process. Among them, platelet-derived growth factor-AB (PDGF-AB) has been reported to be a potent stimulator of angiogenesis in many solid tumours and haematological malignancies, including MM. The aim of the study was to investigate the relationship between PDGF-AB, microvascular density (MVD), and various angiogenic cytokines, such as basic fibroblast growth factor (b-FGF), angiogenin (ANG), and interleukin-6 (IL-6), in MM patients. Forty-seven MM patients before treatment, 22 of whom were in plateau phase, were studied. We determined the serum levels of the aforementioned cytokines and MVD in bone marrow biopsies before and after treatment. Mean serum values of PDGF-AB, b-FGF, ANG, and MVD were significantly higher in patients compared with controls and with increasing disease stage. Significant positive correlations were observed between serum PDGF-AB, ANG, and IL-6 levels and MVD. Furthermore, we found significant positive correlations between PDGF-AB and b-FGF, IL-6, ANG, and β2 microglobulin. We also found that patients with high MVD had statistically significantly higher serum levels of PDGF-AB when a median MVD value of 7.7 was used as the cutoff point. Furthermore, a significant difference was found in serum levels of PDGF-AB between pre- and post-treatment patients. Finally, survival time was significantly higher in the low MVD group versus the high MVD group (76 vs 51 months). Our results showed that there is a strong positive correlation between PDGF-AB and the studied angiogenic cytokines and MVD. It seems that PDGF-AB plays a role in the complex network of cytokines inducing bone marrow neovascularization in patients with MM.     

Brain-derived neurotrophic factor is a potential osteoclast stimulating factor in multiple myeloma

Multiple myeloma (MM) is characterized by accumulation of monoclonal plasma cells in the bone marrow and progression of lytic bone lesions. The mechanisms of enhanced bone resorption in patients with myeloma are not fully defined. We have previously identified the role of brain-derived neurotrophic factor (BDNF) in proliferation and migration of MM cells. In our study, we investigated whether BDNF was possibly involved in MM cell-induced osteolysis. We showed that BDNF was elevated in MM patients and the bone marrow plasma levels of BDNF positively correlated with extent of bone disease. In osteoclast formation assay, bone marrow plasma from patients with MM increased osteoclast formation and the effect was significantly blocked by neutralizing antibody to BDNF, suggesting a critical role for BDNF in osteoclast activation. Furthermore, the direct effects of recombinant BDNF on osteoclast formation and bone resorption support the potential role of BDNF in the MM bone disease. BDNF receptor TrkB was expressed by human osteoclast precursors and a Trk inhibitor K252a markedly inhibited osteoclast formation stimulated with BDNF, demonstrating that BDNF used TrkB for its effects on osteoclast. Finally, bone marrow plasma BDNF level positively correlated with macrophage inflammatory protein-1α and receptor activator of nuclear factor-κB ligand, two major osteoclast stimulatory factors in MM. These results support an important role for BDNF in the development of myeloma bone disease.     

18F-FDG PET/CT对初治多发性骨髓瘤患者预后判断价值分析

目的 正电子发射型计算机断层显像/计算机体层成像(positron emission tomography/computerized tomography,PET/CT)作为一项新兴的核医学技术,将功能代谢及解剖结构显像有机的结合起来,并且在多发性骨髓瘤(multiple myeloma,MM)中的应用也越来越广泛.本研究探讨初治MM患者的18F-脱氧葡萄糖(18-fluorodeoxyglucose,18 F-FDG) PET/CT影像学特征及预后判断价值分析.方法 收集2005-12-01-2015 12 01天津市肿瘤医院并于初治前行PET/CT检查的68例MM患者的基本资料,其中包括病变数目及最大标准化摄取值(maximum standardized uptake value,SUVmax)在内的PET/CT影像特征.采用SPSS 21.0统计软件进行统计学处理,采用Kaplan-Meier法进行生存分析,单因素分析采用Log-rank法,多因素分析采用Cox比例风险模型进行分析.结果 68例初治MM患者,男:女=1.125:1,中位年龄58(22～78)岁.其中骨破坏数量＞3处58例(85.3％),骨破坏区SUVmax＞5.0者26例(38.2％),髓外部位SUVmax＞4.1者12例(17.6％).随访至2016-08,中位随访时间25.3个月.单因素分析显示,血清β2微球蛋白(β2 microglobulin,β2 MG)≥5.5 mg/L(P=0.022)、血清乳酸脱氢酶(lactic dehydrogenase,LDH)＞正常值上限(P=0.023)、PET/CT显示髓外病变(P=0.005)、骨破坏数量＞3处(P=0.036)及治疗结束未达完全缓解(complete remission,CR) (P=0.014)可能为总生存期(overall survival,OS)的不良预后指标.多因素分析显示,初诊时血清β2 MG≥5.5 mg/L(HR=10.076,95％CI为3.8～27.0,P＜0.001)、LDH＞正常值上限(HR=2.327,95％CI为1.0～5.4,P=0.049)、PET/CT存在髓外病变(HR=0.384,95％CI为0.2～0.7,P=0.002)及治疗结束未达CR(HR=3.652,95％CI为1.4～11.6,P=0.028)为初治MM患者不良预后因素.依据上述4个指标,将本研究中68例初治MM患者分为高危组、中危组和低危组,且组间OS差异有统计学意义,P=0.005.结论 PET/CT能结合临床指标在一定程度预测初治MM患者预后生存,具有一定临床价值.     

99Tcm-MDP全身骨显像与全身低剂量CT诊断多发性骨髓瘤的对比研究

目的:通过分析多发性骨髓瘤99Tcm-MDP全身骨显像与全身低剂量CT的影像表现,探讨和比较两者对多发性骨髓瘤(multiple myeloma,MM)辅助诊断、疗效监测和预后判断的应用价值。方法:回顾性分析经骨髓穿刺或手术病理证实的37例MM SPECT全身骨显像和全身低剂量CT的影像表现。结果: 37例MM患者同时行全身骨显像检查及全身低剂量CT检查,两者的阳性率分别为91.9%(34/37)、83.8%(31/37),差异无统计学意义(P>0.05);SPECT联合全身低剂量CT的阳性率为100%(37/37),较单纯SPECT及全身低剂量CT组差异均有统计学意义（P<0.05）,两种方法的总一致性为86.5％。37例MM患者行SPECT检查,发现骨损害总病灶数379个,同期行全身低剂量CT检查,发现骨损害总病灶数189个,全身骨显像显示肋骨病灶的阳性率高于全身低剂量CT（P<0.05）,全身低剂量CT发现颅骨（P<0.05）、四肢骨（P<0.05）和锁骨（P＜0.05）病灶阳性率高于全身骨显像;而脊椎骨、骨盆、胸骨、肩胛骨在全身骨显像和全身低剂量CT上显示的病灶数目无明显差异（P>0.05）。结论:全身骨显像和全身低剂量CT对MM的诊断各有优势,均有一定的临床价值,可作为MM患者的常规检查项目。     

Homing behaviour of the malignant cell clone in multiple myeloma

Multiple myeloma (MM) represents a B cell malignancy characterised by the presence of a monoclonal population of end-stage B cells in the bone marrow. Although fully matured bone marrow plasma cells are the predominant cell type in MM, there is much evidence that also more immature B cells are included in the malignant cell clone which are considered to be the myeloma precursor cells. The fact that these cells are detectable in the blood circulation and that their number increases with disease progression, makes it very likely that they represent the component of the tumour clone that mediates disease dissemination. This implies that these cells must have the potential to extravasate and home to the bone marrow environment. Like the migration mechanisms used by normal leukocytes and/or metastatic tumour cells of non-haematopoietic origin, it can be assumed that this bone marrow homing process is mediated by adhesive interactions and chemotactic signals provided by the microenvironment of the tumour. Once in the bone marrow compartment, myeloma cells will receive the appropriate signals to grow and survive. This aspect of tumour-homing is found to be the result of a functional interplay between the myeloma cells and the surrounding microenvironment, involving the action of several cytokines and adhesion molecules. In the end phase of the disease, myeloma cells can lose their stroma-dependency resulting in extramedullary tumour growth. We review normal B cell homing and discuss molecular mechanisms that determine the homing behaviour of the malignant cell clone in MM.