Department of Hematology, Singapore General Hospital, Outram Road, Singapore, Republic of Singapore.
Am J Hematol. 2010 Oct;85(10):752-6. doi: 10.1002/ajh.21812.
Multiple myeloma is clinically heterogeneous and risk stratification is vital for prognostication and informing treatment decisions. As bortezomib is able to overcome several high-risk features of myeloma, the validity of conventional risk-stratification and prognostication systems needs to be reevaluated. We study the survival data of 261 previously untreated myeloma patients managed at our institution, where bortezomib became available from 2004 for the treatment of relapse disease. Patient and disease characteristics, and survival data were evaluated overall, and with respect to bortezomib exposure. Overall, the international staging system (ISS), metaphase karyotyping and interphase fluorescence in situ hybridization (FISH) were discerning of survival outcomes, where the median for the entire cohort was 5.2 years. However, when stratified by bortezomib exposure, only metaphase karyotyping was still discriminating of long-term prognosis. The presence of an abnormal nonhyperdiploid karyotype overrides all other clinical and laboratory parameters in predicting for a worse outcome on multivariate analysis (median survival 2.6 years, P = 0.001), suggesting that bortezomib used at relapse is better able to overcome adverse risk related to high tumor burden (as measured by the ISS) than adverse cytogenetics on conventional karyotyping. Metaphase karyotyping provides additional prognostic information on tumor kinetics where the presence of a normal diploid karyotype in the absence of any high-risk FISH markers correlated with superior survival and could act as a surrogate for lower plasma cell proliferation.
多发性骨髓瘤在临床上具有异质性，风险分层对于预后判断和治疗决策至关重要。由于硼替佐米能够克服骨髓瘤的多种高危特征，因此需要重新评估传统的风险分层和预后系统的有效性。我们研究了在我们机构接受治疗的 261 例未经治疗的多发性骨髓瘤患者的生存数据，从 2004 年开始，硼替佐米可用于治疗复发性疾病。我们全面评估了患者和疾病特征以及生存数据，并评估了硼替佐米暴露情况。总体而言，国际分期系统（ISS）、中期核型分析和间期荧光原位杂交（FISH）能够区分生存结局，整个队列的中位生存时间为 5.2 年。但是，当按硼替佐米暴露分层时，只有中期核型分析仍然能够区分长期预后。异常非超二倍体核型的存在在多变量分析中可以预测更差的预后（中位生存时间 2.6 年，P = 0.001），这表明硼替佐米在复发时用于治疗能够更好地克服与高肿瘤负荷（如 ISS 所衡量的）相关的不良风险，而不是传统核型分析中的不良细胞遗传学。中期核型分析在肿瘤动力学方面提供了额外的预后信息，在不存在任何高危 FISH 标志物的情况下存在正常二倍体核型与生存状况更好相关，并且可以作为较低浆细胞增殖的替代标志物。
