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Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia
Leukemia ( IF 12.8 ) Pub Date : 2020-03-30 , DOI: 10.1038/s41375-020-0806-0
Tobias Herold , Maja Rothenberg-Thurley , Victoria V. Grunwald , Hanna Janke , Dennis Goerlich , Maria C. Sauerland , Nikola P. Konstandin , Annika Dufour , Stephanie Schneider , Michaela Neusser , Bianka Ksienzyk , Philipp A. Greif , Marion Subklewe , Andreas Faldum , Stefan K. Bohlander , Jan Braess , Bernhard Wörmann , Utz Krug , Wolfgang E. Berdel , Wolfgang Hiddemann , Karsten Spiekermann , Klaus H. Metzeler

The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of acute myeloid leukemia have been widely adopted, but have not yet been validated in large cohorts of AML patients. We studied 1116 newly diagnosed AML patients (age range, 18–86 years) who had received induction chemotherapy. Among 771 patients not selected by genetics, the ELN-2017 classification re-assigned 26.5% of patients into a more favorable or, more commonly, a more adverse-risk group compared with the ELN-2010 recommendations. Forty percent of the cohort, and 51% of patients ≥60 years, were classified as adverse-risk by ELN-2017. In 599 patients <60 years, estimated 5-year overall survival (OS) was 64% for ELN-2017 favorable, 42% for intermediate-risk and 20% for adverse-risk patients. Among 517 patients aged ≥60 years, corresponding 5-year OS rates were 37, 16, and 6%. Patients with biallelic CEBPA mutations or inv(16) had particularly favorable outcomes, while patients with mutated TP53 and a complex karyotype had especially poor prognosis. DNMT3A mutations associated with inferior OS within each ELN-2017 risk group. Our results validate the prognostic significance of the revised ELN-2017 risk classification in AML patients receiving induction chemotherapy across a broad age range. Further refinement of the ELN-2017 risk classification is possible.



中文翻译:

修订后的2017年欧洲白血病的验证和完善急性髓细胞白血病的遗传风险分层

2017年修订的《欧洲白血病网(ELN)》对急性髓样白血病的遗传风险分层建议已被广泛采用,但尚未在大型AML患者队列中得到验证。我们研究了1116例接受诱导化疗的新诊断AML患者(年龄范围18-86岁)。在没有通过遗传学选择的771例患者中,与ELN-2010建议相比,ELN-2017分类将26.5%的患者重新分配为更有利或更常见的更不利风险组。ELN-2017将40%的人群和51%≥60岁的患者归类为不良风险。在599名<60岁患者中,估计的ELN-2017的5年总生存率(OS)为64%,中危为42%,不良风险为20%。在517位年龄≥60岁的患者中,相应的5年OS率分别为37、16和6%。双等位基因患者CEBPA突变或inv(16)的结果特别好,而TP53突变和复杂核型的患者预后特别差。每个ELN-2017风险组中与下等OS相关的DNMT3A突变。我们的结果验证了修订后的ELN-2017风险分类对广泛年龄范围内接受诱导化疗的AML患者的预后意义。可以进一步完善ELN-2017风险分类。

更新日期:2020-04-24
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