Servicio de Hematología, Hospital Universitario de Salamanca, Paseo de San Vicente, 58, Salamanca 37007, Spain.
Cancer J. 2009 Nov-Dec;15(6):457-64. doi: 10.1097/PPO.0b013e3181c51efa.
Multiple myeloma (MM) is an heterogeneous disease and this concept, together with the recent discovery of new drugs with novel mechanisms of action, will lead to the design of individualized treatments. The term "high-risk MM" includes those patients with at least one of the following features: deletion of 17p or t(4;14) or t(14;16), detected by fluorescence in situ hybridization analysis; deletion of 13q detected by conventional cytogenetics; or hypodiploidy or complex karyotype. In addition, patients with high proliferative activity of plasma cells (> or = 3%) measured by the PC labeling index or S-phase by flow cytometry as well as those with a poor response to induction therapy are also high risk. The definition of high-risk MM has been based on patients treated with conventional drugs with or without autologous transplant. However, current data suggest that novel agents can overcome the initial adverse prognosis of deletion 13q and t(4;14) but probably not that of 17p deletion, at least when using immunomodulatory drugs. Nevertheless, the number of patients analyzed is rather limited and, more important, time to progression is only available in a small number of studies. On the basis of these data, it is probably premature to mandate specific therapies on the basis of cytogenetic abnormalities. Moreover, it is possible that the more intensive therapies selected for high-risk patients may be of even greater benefit to standard-risk cases. Accordingly, at present, although we discourage treatment of high-risk patients with conventional schedules, we recommend to include them in large cooperative trials based on novel agents and performing a comprehensive genetic analysis up-front, so that the patients benefiting most from each treatment can subsequently be identified.
多发性骨髓瘤（MM）是一种异质性疾病，这一概念，再加上最近发现具有新型作用机制的新药，将导致设计个体化治疗方案。“高危 MM”一词包括以下至少一种特征的患者：荧光原位杂交分析检测到 17p 缺失或 t（4;14）或 t（14;16）缺失；通过常规细胞遗传学检测到 13q 缺失；或亚二倍体或复杂核型。此外，通过 PC 标记指数或流式细胞术的 S 期测量具有浆细胞高增殖活性（>或= 3%）的患者，以及对诱导治疗反应不佳的患者也是高危患者。高危 MM 的定义是基于接受常规药物联合或不联合自体移植治疗的患者。然而，目前的数据表明，新型药物可以克服 13q 缺失和 t（4;14）的初始不良预后，但可能无法克服 17p 缺失，至少在使用免疫调节药物时是这样。然而，分析的患者数量相当有限，更重要的是，只有少数研究提供了进展时间。基于这些数据，根据细胞遗传学异常强制规定特定的治疗方案可能还为时过早。此外，为高危患者选择更强化的治疗方案可能对标准风险病例更有益。因此，目前，尽管我们不鼓励高危患者使用常规方案进行治疗，但我们建议将他们纳入基于新型药物的大型合作试验，并进行全面的遗传分析，以便随后确定从每种治疗中获益最多的患者。
