Combining information regarding chromosomal aberrations t(4;14) and del(17p13) with the International Staging System classification allows stratification of myeloma patients undergoing autologous stem cell transplantation
Combining information regarding chromosomal aberrations t(4;14) and del(17p13) with the International Staging System classification allows stratification of myeloma patients undergoing autologous stem cell transplantation
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DOI：
10.3324/haematol.2009.016436
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发表时间：
2010-07-01
期刊：
影响因子：
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通讯作者：
Goldschmidt, Hartmut
中科院分区：
文献类型：
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作者：
Neben, Kai;Jauch, Anna;Goldschmidt, Hartmut
背景染色体异常已被证明在多发性骨髓瘤的疾病演变中发挥重要作用。荧光原位杂交可以检测间期细胞的特异性变化，克服了传统细胞遗传学所需的分裂细胞缺乏的问题。设计和方法我们分析了一系列新诊断的有症状多发性骨髓瘤患者（n=315）中荧光原位杂交检测到的12种常见染色体异常的预后价值。所有患者均根据 GMMG-HD3 或 GMMG-HD4 试验方案或类似方案接受一线自体干细胞移植。 结果单变量统计分析显示，del(13q14)、del(17p13)、t(4;14)、+1q21 和非超二倍体的存在与不良无进展生存率和总生存率相关，与国际分期系统 (ISS) 分类无关。多变量分析显示，只有 t(4;14) 和 del(17p13) 保留了无进展生存期和总生存期的预后价值。根据是否存在 t(4;14) 和 del(17p13) 以及患者的国际分期系统分类，队列可分为三个不同的组：预后良好组 [不存在 t(4;14)/del(17p13) 和 ISS I]、预后不良组 [存在 t(4;14)/del(17p13) 和 ISS II/III] 和具有中等预后的组（所有剩余患者）。 5 年总生存率从有利预后组的 72% 降至中间组的 62%（风险比 2.4；P=0.01）和 41%（风险比 5.6；P=0.01）。
BackgroundChromosomal abnormalities have been shown to play a major role in disease evolution of multiple myeloma. Specific changes in interphase cells can be detected by fluorescent in situ hybridization, which overcomes the problem of the lack of dividing cells required for conventional cytogenetics.Design and MethodsWe analyzed the prognostic value of 12 frequent chromosomal abnormalities detected by fluorescent in situ hybridization in a series of patients (n=315) with newly diagnosed, symptomatic multiple myeloma. All patients underwent frontline autologous stem cell transplantation according to the GMMG-HD3- or GMMG-HD4-trial protocols or analogous protocols.ResultsUnivariate statistical analyses revealed that the presence of del(13q14), del(17p13), t(4;14), +1q21 and non-hyperdiploidy was associated with adverse progression-free and overall survival rates independently of the International Staging System (ISS) classification. Multivariate analyses showed that only t(4;14) and del(17p13) retained prognostic value for both progression-free and overall survival. According to the presence or absence of t(4;14) and del(17p13) and the patients' International Staging System classification, the cohort could be stratified into three distinct groups: a group with a favorable prognosis [absence of t(4;14)/del(17p13) and ISS I], a group with a poor prognosis [presence of t(4;14)/del(17p13) and ISS II/III] and a group with an intermediate prognosis (all remaining patients). The probabilities of overall survival at 5 years decreased from 72% in the favorable prognostic group to 62% (hazard ratio 2.4; P=0.01) in the intermediate and 41% (hazard ratio 5.6; P