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[多发性骨髓瘤——诊断检测与治疗的现状]

[Multiple Myeloma - Current Status in Diagnostic Testing and Therapy].

作者信息

Kehrer Michael, Koob Sebastian, Strauss Andreas, Wirtz Dieter Christian, Schmolders Jan

机构信息

Klinik und Poliklinik für Orthopädie und Unfallchirurgie, Universitätsklinikum Bonn.

出版信息

Z Orthop Unfall. 2017 Oct;155(5):575-586. doi: 10.1055/s-0043-110224. Epub 2017 Aug 14.

Abstract

Multiple myeloma is a haematological blood cancer of the bone marrow and is classified by the World Health Organisation (WHO) as a plasma cell neoplasm. In multiple myeloma, normal plasma cells transform into malignant myeloma cells and produce large quantities of an abnormal immunoglobulin called monoclonal protein or M protein. This ultimately causes multiple myeloma symptoms such as bone damage or kidney problems. The annual worldwide incidence of multiple myeloma is estimated to be 6 - 7/100,000 and accounts for 1% of all cancer. In Germany, there are about 6,000 cases of newly diagnosed multiple myeloma per annum. In the current era of new agents, such as immunomodulatory drugs and proteasome inhibitors and antibodies, enormous progress has been achieved in the therapy of multiple myeloma. In orthopaedics, it is essential to be able to recognise the of alarming symptoms of multiple myeloma in clinical routine and to be aware of basic diagnostic features to confirm this disease. Surgical treatment of myeloma-related bone lesions - such as stabilisation of pathological fractures - is an important domain of tumour orthopaedic surgery. A comprehensive literature search was performed in PubMed using the keywords "multiple myeloma" and "diagnostic" or "therapy". This served to evaluate the available primary and secondary literature on the current status of the diagnostic testing and therapy of multiple myeloma. Systematic reviews, meta-analyses and clinical studies as well as international recommendations in therapy were included until the spring of 2016. There are now very sensitive screening methods for the diagnosis of multiple myeloma. Accurate diagnosis is generally based on several factors, including physical evaluation, patient history, symptoms, and diagnostic testing results. The standards for initial diagnostic tests are determined by blood and urine tests as well as a bone marrow biopsy and skeletal imaging, such as X-rays, CT scans and MRI scans. Major and minor criteria are required to confirm the diagnosis of multiple myeloma and help to determine the classification and staging of multiple myeloma, and whether it is smoldering myeloma (asymptomatic), symptomatic myeloma, or a monoclonal gammopathy of undetermined significance (MGUS). Multiple myeloma treatment options have increased significantly over the last 10 years. Standard of basic myeloma treatment consists of high dose chemotherapy in combination with autologous stem cell transplantation. Several factors may determine multiple myeloma treatment, such as age and general health, results of laboratory and cytogenetic (genomic) tests as well as symptoms and disease complications. After evaluation of these factors, an individual and often multimodal treatment plan is created and implemented in interdisciplinary cooperation. Conventional treatment options have to be evaluated for older patients (> 70 - 75 years), who are not eligible for high dose chemotherapy and autologous stem cell transplantation due to their age and/or severe comorbidities. It is essential to include supportive therapy in the integral treatment concept, in order to control pain or retain function or mobility. Supportive drugs such as bisphosphonates but also radiation therapy and orthopaedic surgery may be required in order to manage complications of the disease as well as side effects of treatment. Current studies show promising results in the treatment of multiple myeloma, due to new agents such as immunomodulatory drugs, proteasome inhibitors and antibodies, which may improve prognosis and survival rate among myeloma patients in the future. However treatment algorithms have become more complex and expensive.

摘要

多发性骨髓瘤是一种发生于骨髓的血液系统恶性肿瘤,世界卫生组织(WHO)将其归类为浆细胞肿瘤。在多发性骨髓瘤中,正常浆细胞转变为恶性骨髓瘤细胞,并产生大量异常免疫球蛋白,称为单克隆蛋白或M蛋白。这最终会引发多发性骨髓瘤的症状,如骨损伤或肾脏问题。全球多发性骨髓瘤的年发病率估计为6-7/10万,占所有癌症的1%。在德国,每年约有6000例新诊断的多发性骨髓瘤病例。在当前免疫调节药物、蛋白酶体抑制剂和抗体等新型药物的时代,多发性骨髓瘤的治疗取得了巨大进展。在骨科领域,临床工作中必须能够识别多发性骨髓瘤的警示症状,并了解基本的诊断特征以确诊该病。骨髓瘤相关骨病变的外科治疗,如病理性骨折的固定,是肿瘤骨科手术的一个重要领域。 使用关键词“多发性骨髓瘤”和“诊断”或“治疗”在PubMed上进行了全面的文献检索。这有助于评估关于多发性骨髓瘤诊断检测和治疗现状的现有一级和二级文献。纳入了系统评价、荟萃分析和临床研究以及2016年春季之前的国际治疗推荐。 现在有非常敏感的筛查方法用于诊断多发性骨髓瘤。准确的诊断通常基于几个因素,包括体格检查、患者病史、症状和诊断检测结果。初始诊断测试的标准由血液和尿液检测以及骨髓活检和骨骼成像确定,如X线、CT扫描和MRI扫描。确诊多发性骨髓瘤需要主要和次要标准,这有助于确定多发性骨髓瘤的分类和分期,以及它是冒烟型骨髓瘤(无症状)、有症状骨髓瘤还是意义未明的单克隆丙种球蛋白病(MGUS)。在过去10年中,多发性骨髓瘤的治疗选择显著增加。骨髓瘤基本治疗的标准包括高剂量化疗联合自体干细胞移植。几个因素可能决定多发性骨髓瘤的治疗,如年龄和总体健康状况、实验室和细胞遗传学(基因组)检测结果以及症状和疾病并发症。在评估这些因素后,制定并通过多学科合作实施个体化且通常是多模式的治疗方案。对于因年龄和/或严重合并症而不符合高剂量化疗和自体干细胞移植条件的老年患者(>70-75岁),必须评估传统治疗方案。在整体治疗理念中纳入支持性治疗至关重要,以控制疼痛或保留功能或活动能力。可能需要使用双膦酸盐等支持性药物以及放疗和骨科手术来处理疾病并发症以及治疗的副作用。 当前的研究表明,由于免疫调节药物、蛋白酶体抑制剂和抗体等新型药物,多发性骨髓瘤的治疗取得了有前景的结果,并可能在未来改善骨髓瘤患者的预后和生存率。然而,治疗方案变得更加复杂且昂贵。

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