Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205-7199, USA.
Haematologica. 2012 Nov;97(11):1761-7. doi: 10.3324/haematol.2012.065698. Epub 2012 Jun 11.
Extramedullary disease is an uncommon manifestation in multiple myeloma and can either accompany newly diagnosed disease or develop with disease progression or relapse. We evaluated the impact of this disease feature on patients' outcome in the context of novel agents.
We analyzed clinical and biological features of extramedullary disease in 936 patients with multiple myeloma enrolled in Total Therapy protocols, 240 patients in non-Total Therapy protocols, and 789 non-protocol patients, all of whom had baseline positron emission tomography scans to document extramedullary disease at diagnosis and its subsequent development at the time of disease progression or relapse.
The most common sites for extramedullary disease at diagnosis were skin and soft tissue whereas liver involvement was the striking feature in extramedullary disease at disease relapse or progression. Regardless of therapy, extramedullary disease was associated with shorter progression-free and overall survival, as well as the presence of anemia, thrombocytopenia, elevated serum lactate dehydrogenase, cytogenetic abnormalities, and high-risk features in 70-and 80-gene risk models in univariate analysis. Multivariate analysis with logistic regression revealed that this disease feature was more prevalent in patients with an elevated centrosome index, as determined by gene expression profiling, as well as in myeloma molecular subtypes that are more prone to relapse. These include the MF subtype (also called the "MAF" subtype, associated with over-expression of the MAF gene seen with chromosome translocation 14;16 or 14;20) and the PR subtype (also called the "Proliferation" subtype, associated with overexpression of pro-proliferative genes).
These data show that extramedullary disease is more prevalent in genomically defined high-risk multiple myeloma and is associated with shorter progression-free survival and overall survival, even in the era of novel agents. All clinical trials included in the analyses were registered with www.clinicaltrials.gov (NCT00083551, NCT00083876, NCT00081939, NCT00572169, NCT00644228,NCT00002548,NCT00734877).
髓外疾病是多发性骨髓瘤的一种罕见表现，可与新诊断的疾病同时发生，也可随着疾病的进展或复发而发生。我们评估了这种疾病特征在新型药物治疗背景下对患者预后的影响。
我们分析了 936 例多发性骨髓瘤患者（均接受了总治疗方案）、240 例未接受总治疗方案的患者和 789 例非方案患者的髓外疾病的临床和生物学特征，所有患者在诊断时均进行了正电子发射断层扫描（PET）以记录髓外疾病，并在疾病进展或复发时记录其随后的发展情况。
髓外疾病最常见的部位是皮肤和软组织，而肝脏受累是髓外疾病在疾病复发或进展时的显著特征。无论治疗方法如何，髓外疾病均与无进展生存期和总生存期缩短以及贫血、血小板减少、血清乳酸脱氢酶升高、细胞遗传学异常和 70 基因和 80 基因风险模型中的高危特征相关，这在单因素分析中得到了证实。多因素逻辑回归分析显示，该疾病特征在通过基因表达谱确定的中心体指数升高的患者以及更易复发的骨髓瘤分子亚型患者中更为常见。这些亚型包括 MF 亚型（也称为“MAF”亚型，与染色体易位 14；16 或 14；20 相关，可见 MAF 基因过度表达）和 PR 亚型（也称为“增殖”亚型，与促增殖基因过度表达相关）。
这些数据表明，髓外疾病在基因组定义的高危多发性骨髓瘤中更为常见，并且即使在新型药物治疗时代，也与无进展生存期和总生存期缩短相关。分析中包括的所有临床试验均在 www.clinicaltrials.gov 上注册（NCT00083551、NCT00083876、NCT00081939、NCT00572169、NCT00644228、NCT00002548、NCT00734877）。
