Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome
Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myelome
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DOI：
10.1182/blood-2006-08-040410
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发表时间：
2007-04-15
期刊：
影响因子：
20.3
通讯作者：
Mathiot, Claire
中科院分区：
文献类型：
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作者：
Avet-Loiseau, Herve;Attal, Michel;Mathiot, Claire
获得性基因组畸变已被证明会显着影响几种血液恶性肿瘤的生存。我们分析了前瞻性纳入同质治疗试验的大量新诊断症状性骨髓瘤患者中最常见的染色体变化的预后价值。参加 Intergroupe Francophone du Myelome 进行的 IFM99 试验的所有 1064 名患者均受益于对纯化的骨髓浆细胞进行的间期荧光原位杂交分析。他们系统地筛选了以下基因组畸变：del(13)、t(11;14)、t(4;14)、超二倍体、MYC 易位和 del(17p)。 90%的患者观察到染色体变化。 del(13)、t(11;14)、t(4;14)、超二倍体、MYC 易位和 del(17p) 分别存在于 48%、21%、14%、39%、13% 和 11% 的患者中。中位随访 41 个月后，单变量统计分析显示 del(13)、t(4;14)、非超二倍体和 del(17p) 对无事件生存率和总生存率均产生负面影响，而 t(11;14) 和 MYC 易位不影响预后。对 513 名注释所有参数的患者进行的多变量分析表明，只有 t(4;14) 和 del(17p) 保留了无事件生存率和总生存率的预后价值。与目前使用的国际分期系统相比，该预后模型具有优势。在骨髓瘤中，基因组畸变 t(4;14) 和 del(17p) 以及 β2-微球蛋白水平是生存的重要独立预测因子。这些发现对于风险适应治疗策略的设计具有重要意义。
Acquired genomic aberrations have been shown to significantly impact survival in several hematologic malignancies. We analyzed the prognostic value of the most frequent chromosomal changes in a large series of patients with newly diagnosed symptomatic myeloma prospectively enrolled in homogeneous therapeutic trials. All the 1064 patients enrolled in the IFM99 trials conducted by the Intergroupe Francophone du Myelome benefited from an interphase fluorescence in situ hybridization analysis performed on purified bone marrow plasma cells. They were systematically screened for the following genomic aberrations: del(13), t(11;14), t(4; 14), hyperdiploidly, MYC translocations, and del(17p). Chromosomal changes were observed in 90% of the patients. The del(13), t(11;14), t(4;14), hyperdiploidy, MYC translocations, and del(17p) were present in 48%, 21%, 14%, 39%, 13%, and 11% of the patients, respectively. After a median follow-up of 41 months, univariate statistical analyses revealed that del(13), t(4;14), nonhyperdiploidy, and del(17p) negatively impacted both the event-free survival and the overall survival, whereas t(11;14) and MYC-translocations did not influence the prognosis. Multivariate analyses on 513 patients annotated for all the parameters showed that only t(4;14) and del(17p) retained prognostic value for both the event-free and overall survivals. When compared with the currently used International Staging System, this prognostic model compares favorably. In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta 2-microglobulin level, are important independent predictors of survival. These findings have implications for the design of risk-adapted treatment strategies.