多发性骨髓瘤的预后评估与危险分层治疗

 新的靶向治疗药物（沙利度胺、硼替佐米、雷利度胺、砷剂）治疗MM取得了突破性进展,明显改善了MM的预后。MM的临床异质性是由生物学特性所决定的,正确地评估患者的预后,对不同患者进行分层治疗极为重要。     

多发性骨髓瘤细胞遗传学异常研究进展

 随着细胞遗传学和分子生物学技术的迅速发展,人们对多发性骨髓瘤（MM）中细胞遗传学异常的认识逐渐加深。MM细胞遗传学异常以非整倍体核型、13号染色体异常、Ig易位等为主,具有独特的分子生物学改变,与疾病的临床特点密切相关。对此领域进行深入探讨,将有助于我们了解MM的发生、发展机制,建立更合理有效的诊治策略。     

多发性骨髓瘤的靶向治疗

 在过去的近10年中,尽管多发性骨髓瘤（MM）的治疗取得了较大进步,患者的缓解率明显提高,但总的生存期（OS）没有明显改善。随着对MM发病机制研究的深入,以沙利度胺和硼替佐米为代表的靶向治疗药物的应用,使MM的完全缓解率明显提高,OS得到延长,MM成为一种趋于治愈性的疾病。     

多发性骨髓瘤的靶向治疗

 阐述抑制蛋白酶体是癌症治疗一种新方法。波替单抗（商品名：万珂）是第一个批准临床应用的蛋白酶体抑制剂。临床前试验对许多肿瘤细胞株有效。Ⅰ期临床试验确定了最佳剂量与可处理的毒性。两个Ⅱ期试验（SUMMIT与CREST）证明万珂治疗复发和／或难治的骨髓瘤患者安全而有效。Ⅲ期APEX试验比较万珂与大剂量地塞米松治疗复发的骨髓瘤证实万珂能提高有效率、缓解持续时间和总生存期。据此，研究者探索万珂与常规化疗和其他新药的联合。继续进行中的试验用万珂作为第一线药物治疗骨髓瘤结果令人鼓舞。单用万珂与其联合方案治疗血液与实体恶性肿瘤值得进一步研究。     

多发性骨髓瘤的免疫表型特征

 目的 研究多发性骨髓瘤（MM）细胞的免疫表型特征,以期为多发性骨髓瘤的诊断、预后判断和治疗监测提供可靠的依据。方法 采用多参数流式细胞术,对55例MM患者和6例正常人骨髓细胞利用CD45PE-cy5／SS设门,在EPICS XL流式细胞仪上获取3×104个细胞,分析各群细胞CD10,CD20,CD38,CD56,CD19,CD138,CD34,CD13,CD7,CD33的表达。结果 55例MM患者的CD138,CD38,CD56,CD20,CD19,CD13和CD33分别表达为100 %,81.8 %,20.0 %,3.6 %,10.9 %和21.8 %;CD45一般为阴性或弱阳性;其他标志均为阴性。结论 多参数流式细胞术免疫表型分析在MM的辅助诊断、预后评估以及治疗监测方面是一项非常重要的技术。     

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。     

多发性骨髓瘤的治疗现状

 多发性骨髓瘤（MM）的治疗取得了突破性进展。20世纪90年代开始,应用造血干细胞移植治疗MM明显提高了疗效,中位总生存期达到5年。近年来,随着多种靶位治疗药物（沙利度胺、硼替佐米、雷利度胺）的临床应用,使得各类型骨髓瘤的预后有了显著改善,据统计中位总生存期又提升了50 %。临床资料最新估计,65岁以下患者中位生存期约为10年,老年患者约5～6年。目前正在研制的新药物必将进一步提高患者的疗效。     

Hemibody irradiation in multiple myeloma

Eighteen patients with multiple myeloma were treated by hemibody irradiation using large single fractions, usually to a dose of 10 Gy (lower half) and 7.5 Gy (upper half). All except one patient had previously been treated by multiple courses of conventional chemotherapy with melphalan and prednisone, and were considered to be resistant to further chemotherapy. In most cases, local field irradiation had also been given for symptomatic bone pain. Of the 13 patients who had symptoms at the start of hemibody irradiation, 11 improved sufficiently for their analgesia requirement to be reduced. In eight patients, there was a significant fall in circulating immunoglobulin but no patient with Bence-Jones proteinuria had complete resolution of this biochemical abnormality. Although thrombocytopenia and neutropenia were common, only two patients required platelet transfusion and the treatment was in general extremely well tolerated. Survival following hemibody irradiation was similar to the survival reported from the use of "second-line" chemotherapy and we feel that hemibody irradiation is a more acceptable alternative for most patients.     

多发性骨髓瘤的基本治疗策略

随着医学诊断水平的提高和人口的老龄化,多发性骨髓瘤（MM）的发病率也逐年提高。当前MM仍被认为是一种不可治愈的疾病,因此,努力提高诊断水平,认真地研究合理的治疗方法,特别是近年来倡导的新药与传统药物的联合治疗、危险分层的治疗以及个体化治疗,是延长生存期、减少并发症、改善预后的重要途径。     

多发性骨髓瘤相关微小RNA的研究进展

微小RNA（miRNA）是一类非编码的小分子RNA,其可通过抑制特异靶基因的翻译或直接降解靶基因,实现基因的转录后调控.大量研究显示,miRNA的异常表达与多系统肿瘤相关,对多发性骨髓瘤（MM）的研究发现,miRNA的异常表达参与了MM细胞的增殖、分化、凋亡及耐药等过程,并可作为MM的诊断标志物;某些miRNA甚至可能作为MM的有效治疗靶点.文章就MM相关miRNA的异常表达与MM的诊断、发病机制、耐药形成及其作为治疗靶点潜力的研究进展进行综述.     

初发多发性骨髓瘤的治疗进展

多发性骨髓瘤（MM）是一种恶性浆细胞肿瘤。MM患者大多数年龄超过65岁,目前认为65岁以下初发MM患者的标准治疗为大剂量美法仑化疗支持的自体干细胞移植（ASCT）,而65岁以上老年MM患者的标准治疗至今仍认为是口服美法仑和泼尼松（MP）方案。但是一些新药的发明,如沙利度胺、雷利度胺和蛋白酶体抑制剂硼替佐米,能针对骨髓瘤细胞和骨髓微环境进行靶向治疗,联合使用在很大程度上能提高以往化疗方案的临床疗效。     

多发性骨髓瘤的治疗进展

目的 多发性骨髓瘤(mutciple myelome,MM)是血液系统恶性肿瘤,近年来,MM的治疗已经取得了显著的进展.一些新药沙利度胺、硼替佐米、雷利度胺的应用扩大了MM患者的治疗选择并改善了预后.大量的Ⅲ期临床实验已经表明了新药联合治疗移植和非移植患者的有效性,基于这些研究结果,标准的诱导方案已经受到挑战、甚至被取代.对于适合移植的患者,一些新的诱导缓解方案的有效性优于长春新碱+多柔比星+地塞米松(VAD)方案.同样,对于不适合移植的患者,联合这些新药的一线治疗也被证明优于传统的马法兰+泼尼松(MP)方案.现基于新药的联合治疗策略就MM的治疗进展进行综述.     

多发性骨髓瘤的治疗

异基因造血干细胞移植是惟一有可能治愈多发性骨髓瘤的方法,但其治疗相关死亡率高限制了其应用。自体造血干细胞移植对提高患者的生活质量及延长生存期起到了巨大的作用,近年来各种新药及传统的化疗方案加新药所组成的新的化疗方案的应用更进一步提高了自体造血干细胞移植的疗效。     

多发性骨髓瘤的治疗

异基因造血干细胞移植是惟一有可能治愈多发性骨髓瘤的方法,但其治疗相关死亡率高限制了其应用.自体造血干细胞移植对提高患者的生活质量及延长生存期起到了巨大的作用,近年来各种新药及传统的化疗方案加新药所组成的新的化疗方案的应用更进一步提高了自体造血干细胞移植的疗效.     

多发性骨髓瘤分型的进展

 关于多发性骨髓瘤的分型,目前临床上常规根据其分泌M蛋白成分的不同进行分型,并依据Durie-Salmon 分期标准和ISS分期系统进行分期。此外,人们还根据骨髓瘤细胞染色体的异常以及荧光原位杂交（FISH）检测的结果进行分型,其中最常见的细胞遗传学异常有del(13), t(4;14)(p16;q32), del 17p等。随着比较基因组杂交（CGH）、FISH 及基因表达谱等分子生物学研究技术的进步和广泛运用,人们正在探索诸如TC分期系统,UAMS分子分期系统及基因表达谱预后模型以提示多发性骨髓瘤的预后和指导治疗。     

Non-random chromosomal aberrations associated with multiple myeloma

Myelomatous tissue from 30 patients was assessed for cytogenetic abnormalities and one-third showed chromosomal deletions, additions, and/or rearrangements. Evidence is presented that those cases with only normal cytogenetics represent metaphase cells of nonmyelomatous tissue. The findings of our abnormal cases when added to the 18 reported in two series by others show unique cytogenetic patterns are present in this disease. From analysis of these 27 banded cases of myeloma, we conclude: (1) cytogenetic abnormalities of myeloma are not random; (2) clonal evolution may be associated with disease progression, however the abnormalities identified late in the disease are similar to those found in early myeloma; (3) cytogenetic aberrations of multiple myeloma differ considerably from those of chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and acute lymphocytic and nonlymphocytic leukemia; and (4) the myeloma karyotype often exhibits one or more of the following: rearrangements involving chromosome 1 and 14, trisomy 3, 5, 7, 9 and 11, and monosomy 8 and 13. These findings have great importance for molecular biologic studies of multiple myeloma.     

In vitro growth of hematopoietic progenitors and stromal bone marrow cells from patients with multiple myeloma

In the present study we have determined the content of hematopoietic and stromal progenitors in multiple myeloma (MM) bone marrow, and assessed their in vitro growth. Marrow cells were obtained from 17 MM patients at the time of diagnosis, and from 6 hematologically normal subjects. When mononuclear cells (MNC) from MM marrow were cultured, reduced numbers of hematopoietic progenitors were detected and their growth in long-term cultures was deficient, as compared to cultures of normal cells. When cell fractions enriched for CD34⁺ Lin⁻ cells were obtained, the levels of hematopoietic progenitors from MM marrow were within the normal range, and so was their growth kinetics in liquid suspension cultures. The levels of fibroblast progenitors in MM were not statistically different from those in normal marrow; however, their proliferation potential was significantly reduced. Conditioned media from MM-derived MNC and stroma cells contained factors that inhibited normal progenitor cell growth. Our observations suggest that hematopoietic progenitors in MM marrow are intrinsically normal; however, their growth in LTMC may be hampered by the presence of abnormal accessory and stroma cells. These results suggest that besides its role in the generation of osteolytic lesions and the expansion of the myeloma clone, the marrow microenvironment in MM may have a negative effect on hematopoiesis.     

单克隆抗体在多发性骨髓瘤治疗中的应用

新药的应用使多发性骨髓瘤(MM)患者生存期显著延长,但部分患者在治疗过程中出现耐药.单克隆抗体治疗MM作为一种新方案,可使部分患者获益.文章对单克隆抗体治疗MM的研究进展进行综述.     

多发性骨髓瘤的诊断及免疫治疗研究进展

多发性骨髓瘤(MM)发病机制研究的深入及新药的广泛应用,对MM的检测手段及疗效评价提出了进一步的要求。2018年美国血液学会(ASH)年会中推荐使用低剂量CT而不是普通X线片作为初诊MM患者的骨骼是否累及的筛查;治疗方面,单抗在MM治疗中的地位得到进一步巩固,嵌合抗原受体T细胞(CAR-T)治疗全面发展。     

多发性骨髓瘤患者血栓形成与防治

 【摘要】 在多发性骨髓瘤（MM）患者中,静脉血栓栓塞症的发生率远高于健康人群。就MM患者中血栓形成的机制、相关危险因素、治疗、预防等方面的一些研究进展作一综述。