Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System
Prediction of high- and low-risk multiple myeloma based on gene expression and the International Staging System
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DOI：
10.1182/blood-2015-05-644039
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发表时间：
2015-10-22
期刊：
影响因子：
20.3
通讯作者：
Sonneveld, Pieter
中科院分区：
文献类型：
--
作者：
Kuiper, Rowan;van Duin, Mark;Sonneveld, Pieter
多发性骨髓瘤患者的生存率存在差异，需要可靠的预后和预测评分系统。目前，临床和生物风险标记物是独立使用的。在这里，国际分期系统 (ISS)、荧光原位杂交 (FISH) 标记和基因表达 (GEP) 分类器相结合，以在发现/验证环境中识别新的风险分类。我们使用了荷兰-比利时血液肿瘤学组和德语骨髓瘤多中心组 (HO65/GMMG-HD4)、阿肯色大学医学科学大学-TT2 (UAMS-TT2)、UAMS-TT3、医学研究委员会-IX、延长缓解期的蛋白酶体抑制评估和骨髓法语组间 (IFM-G) 的数据集（患者总数：第4750章）评估了 20 个风险标记，包括 t(4;14) 和 17p 缺失 (FISH)、EMC92 和 UAMS70（GEP 分类器）以及 ISS。新颖的风险分类表明 ISS 是 GEP 分类器和 FISH 的宝贵合作伙伴。对所有新的和现有的风险分类进行排名表明，EMC92-ISS 组合是总体生存率最强的预测因子，从而形成 4 组风险分类。最高风险组的中位生存期为24个月，中等风险组为47个月和61个月，最低风险组的中位生存期为96个月后仍未达到。 EMC92-ISS 分类是一种基于生物学和临床参数的新型预后工具，优于当前的标志物，并提供稳健的、临床相关的 4 组模型。
Patients with multiple myeloma have variable survival and require reliable prognostic and predictive scoring systems. Currently, clinical and biological risk markers are used independently. Here, International Staging System (ISS), fluorescence in situ hybridization (FISH) markers, and gene expression (GEP) classifiers were combined to identify novel risk classifications in a discovery/validation setting. We used the datasets of the Dutch-Belgium Hemato-Oncology Group and German-speaking Myeloma Multicenter Group (HO65/GMMG-HD4), University of Arkansas for Medical Sciences-TT2 (UAMS-TT2), UAMS-TT3, Medical Research Council-IX, Assessment of Proteasome Inhibition for Extending Remissions, and Intergroupe Francophone du Myelome (IFM-G) (total number of patients: 4750). Twenty risk markers were evaluated, including t(4;14) and deletion of 17p (FISH), EMC92, and UAMS70 (GEP classifiers), and ISS. The novel risk classifications demonstrated that ISS is a valuable partner to GEP classifiers and FISH. Ranking all novel and existing risk classifications showed that the EMC92-ISS combination is the strongest predictor for overall survival, resulting in a 4-group risk classification. The median survival was 24 months for the highest risk group, 47 and 61 months for the intermediate risk groups, and the median was not reached after 96 months for the lowest risk group. The EMC92-ISS classification is a novel prognostic tool, based on biological and clinical parameters, which is superior to current markers and offers a robust, clinically relevant 4-group model.