Schnittger Susanne, Weisser Martin, Schoch Claudia, Hiddemann Wolfgang, Haferlach Torsten, Kern Wolfgang
Laboratory for Leukemia Diagnostics, Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University, Marchioninistrasse 15, 81377 Munich, Germany.
Blood. 2003 Oct 15;102(8):2746-55. doi: 10.1182/blood-2003-03-0880. Epub 2003 Jul 3.
To evaluate the prognostic significance of quantitative PML-RARA, AML1-ETO, and CBFB-MYH11 fusion transcript expression, real-time polymerase chain reaction was used to analyze bone marrow samples of 349 such patients at diagnosis and 522 samples of 142 patients also during therapy (total analyses, n = 859; median number of follow-up samples, 4/patient; median duration of assessment, 12 months). Lower expression levels at diagnosis correlated with better overall and event-free survival in all 3 leukemia subtypes. By combining the median expression ratio after consolidation therapy and the 75th percentile of the expression ratio at diagnosis, a new score was established that separates a group with 100% EFS from a significantly worse group (P <.0001) in each of the 3 acute myeloid leukemia subgroups. Eight patients showed increasing levels of expression during follow-up and all had relapse. In conclusion, patients at high risk for treatment failure can be identified by high levels of fusion gene expression at diagnosis or less than 3 logs of tumor reduction during the first 3 to 4 months of therapy. By combining the transcription ratios at these 2 checkpoints, a new powerful prognostic score has been established.
为评估定量PML-RARA、AML1-ETO和CBFB-MYH11融合转录本表达的预后意义,采用实时聚合酶链反应分析了349例此类患者诊断时的骨髓样本以及142例患者治疗期间的522份样本(总计分析样本859份;每位患者随访样本中位数为4份;评估中位持续时间为12个月)。在所有3种白血病亚型中,诊断时较低的表达水平与较好的总生存期和无事件生存期相关。通过结合巩固治疗后的中位表达率和诊断时表达率的第75百分位数,建立了一个新的评分系统,该系统在3个急性髓系白血病亚组中均能将无事件生存期为100%的一组与明显较差的一组区分开来(P <.0001)。8例患者在随访期间表达水平升高,均复发。总之,治疗失败高风险患者可通过诊断时融合基因高表达或治疗前3至4个月内肿瘤缩小少于3个对数来识别。通过结合这两个检查点的转录率,建立了一个新的强大的预后评分系统。