2014年意义未明的单克隆丙种球蛋白病及无症状多发性骨髓瘤
[Monoclonal gammopathy of undetermined significance and asymptomatic multiple myelom in the year 2014 ].
作者信息
Adam Zdeněk, Krejčí Marta, Pour Luděk, Sevčíková Eva, Křivanová Andrea, Rehák Zdeněk, Koukalová Renata, Cermáková Zdeňka, Vaníček Jíří, Sevčíková Sabina
出版信息
Vnitr Lek. 2014 Oct;60(10):861-79.
Presence of monoclonal immunoglobulin in serum or urine is a relatively common event affecting about 3.2 % of people over 50. Isolated increase of only one type of free light chain, either κ or λ, is detected in 0.7-0.8 % of people over 50. Most people with monoclonal immunoglobulin meet the criteria of the so-called "mono-clonal gammopathy of undetermined significance (MGUS)". MGUS is defined by concentration of monoclonal immunoglobulin in serum < 30 g/l, number of plasma cells in the bone marrow < 10 % and the absence of symptoms of multiple myeloma and other lymphoproliferative diseases. A proportion of people with MGUS gradually progresses from asymptomatic into symptomatic myeloma or other malignant lymphoproliferative disease requiring treatment. Therefore, MGUS is considered to be one of the most common premalignant conditions with an average risk of transformation into malignant disease of 1 % per year. Monoclonal gammopathy of IgG and IgA subtype can develop into multiple myeloma. Light chain monoclonal gammopathy can develop not only into light chain multiple myeloma but also into AL-amyloidosis and light chain deposition disease (amorphous deposits of light chains damaging organs). IgM monoclonal gammopathy may develop into Waldenstrom macroglobulinemia or other lymphoproliferative disorder, or into rare IgM subtype of multiple myeloma. Unfortunately, people with MGUS are threatened by more than an increased risk of transformation into multiple myeloma or other severe hematologic disease. Pre-malignant clone of plasma cells in the bone marrow causes changes in the bone marrow that directly affect the person. For people with MGUS, there is an increased incidence of osteoporosis and increased fracture risk when compared to the general population. People with MGUS also have an increased risk of bacterial infections and thromboembolic complications compared with the same age population without MGUS. Clonal plasma cells, which are the basis of MGUS, may in some cases produce toxic monoclonal immunoglobulin which can damage the body's own antibody activity by binding to specific antigens (such as cold agglutinin disease), or their deposits in organs (e.g. kidney damage) or physical properties (e.g. cryoglobulinemia). Therefore, it is recommended that this group of people is regularly checked with the aim to capture not only transformation into symptomatic multiple myeloma or another malignant disease, but also the formation of the above-mentioned complications. Moreover, it is recommended to monitor patients with asymptomatic myeloma and to initiate treatment only after symptoms of multiple myeloma are observed. In 2014, discussion of subdivision of subgroups of patients with asymptomatic myeloma with high ( 80 %) probability of early (within 2 years) transformation in multiple myeloma which would be beneficial for early initiation of treatment is ongoing. According to first proposals, patients with asymptomatic myeloma that meet at least one of the three conditions: more than 60 % of plasma cells in the bone marrow, ratio of free light kappa and lambda chains is greater than 100 or less than 0.01, or multiple focal lesions on whole-body MRI of the skelet. The review contains current opinions on prognostic classification and appropriate intervals and extent of control examinations.
血清或尿液中存在单克隆免疫球蛋白是一种相对常见的现象,影响着约3.2%的50岁以上人群。在50岁以上人群中,0.7 - 0.8%的人检测到仅一种游离轻链(κ或λ)单独升高。大多数单克隆免疫球蛋白患者符合所谓“意义未明的单克隆丙种球蛋白病(MGUS)”的标准。MGUS的定义为血清中单克隆免疫球蛋白浓度<30 g/l、骨髓中浆细胞数量<10%且无多发性骨髓瘤和其他淋巴增殖性疾病的症状。一部分MGUS患者会逐渐从无症状状态进展为有症状的骨髓瘤或其他需要治疗的恶性淋巴增殖性疾病。因此,MGUS被认为是最常见的癌前疾病之一,每年转化为恶性疾病的平均风险为1%。IgG和IgA亚型的单克隆丙种球蛋白病可发展为多发性骨髓瘤。轻链单克隆丙种球蛋白病不仅可发展为轻链多发性骨髓瘤,还可发展为AL型淀粉样变性和轻链沉积病(轻链无定形沉积物损害器官)。IgM单克隆丙种球蛋白病可能发展为华氏巨球蛋白血症或其他淋巴增殖性疾病,或发展为罕见的IgM亚型多发性骨髓瘤。不幸的是,MGUS患者面临的威胁不仅仅是转化为多发性骨髓瘤或其他严重血液系统疾病的风险增加。骨髓中的癌前浆细胞克隆会导致骨髓发生变化,直接影响患者。与普通人群相比,MGUS患者骨质疏松的发生率增加,骨折风险也增加。与同龄无MGUS的人群相比,MGUS患者发生细菌感染和血栓栓塞并发症的风险也增加。作为MGUS基础的克隆性浆细胞在某些情况下可能产生有毒的单克隆免疫球蛋白,其可通过与特定抗原结合(如冷凝集素病)损害机体自身抗体活性,或在器官中沉积(如肾损害)或改变物理性质(如冷球蛋白血症)。因此,建议对这组人群定期进行检查,目的不仅是发现向有症状的多发性骨髓瘤或其他恶性疾病的转化,还要发现上述并发症的形成。此外,建议对无症状骨髓瘤患者进行监测,仅在观察到多发性骨髓瘤症状后才开始治疗。2014年,关于对无症状骨髓瘤患者亚组进行细分的讨论正在进行,这些患者早期(2年内)转化为多发性骨髓瘤的概率较高(80%),这将有利于早期开始治疗。根据初步提议,无症状骨髓瘤患者符合以下三个条件中的至少一个:骨髓中浆细胞超过60%、游离轻链κ和λ链的比值大于100或小于0.01或全身骨骼MRI有多发病灶。该综述包含了关于预后分类以及合适的检查间隔和范围的当前观点。