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Targeted Sequencing Improves DIPSS-Plus Prognostic Scoring in Myelofibrosis Patients Undergoing Allogeneic Transplantation.
Biology of Blood and Marrow Transplantation ( IF 5.609 ) Pub Date : 2020-03-16 , DOI: 10.1016/j.bbmt.2020.03.007
Emily A Stevens 1 , Isaac C Jenkins 2 , Lan W Beppu 3 , Qing Zhang 4 , Rachel Salit 1 , Keith R Loeb 5 , H Joachim Deeg 1 , Jerald P Radich 6
Affiliation  

Primary myelofibrosis (MF) and secondary MF developing after polycythemia vera or essential thrombocythemia are clonal disorders of hematopoiesis. Currently the sole therapy offering the potential of cure is hematopoietic cell transplantation (HCT). Several risk classification systems including clinical, hematologic, and mutational parameters have been proposed. We analyzed the mutational landscape in addition to the Dynamic International Prognostic Scoring System (DIPSS)-plus in 55 patients with MF to determine the combined impact on post-HCT outcome. Mutations, analyzed in 75 genes, were most common in JAK2, CALR, ASXL1, TET2, GATA2, EZH2, U2AF1, and ETV6. Patients with ≥3 mutations in addition to JAK2 or CALR mutations had a higher post-transplantation relapse rate and nonrelapse mortality than patients with fewer mutations, independent of DIPSS-plus risk. The presence of higher numbers of mutations identified patients at the greatest risk of relapse within the highest overall risk group as determined by DIPSS-plus. These findings are consistent with molecular risk classifications for patients who do not undergo HCT and support the proposed transplantation risk classification incorporating mutational information.



中文翻译:

靶向测序可改善接受异基因移植的骨髓纤维化患者的DIPSS-Plus预后评分。

真性红细胞增多症或原发性血小板增多症后发展为原发性骨髓纤维化(MF)和继发性MF是造血功能性克隆疾病。目前,唯一具有治愈潜力的疗法是造血细胞移植(HCT)。已经提出了几种风险分类系统,包括临床,血液学和突变参数。除了动态国际预后评分系统(DIPSS)-plus,我们还分析了55名MF患者的突变情况,以确定对HCT后结果的综合影响。在75个基因中进行分析的突变在JAK2,CALR,ASXL1,TET2,GATA2,EZH2,U2AF1ETV6中最为常见。除JAK2CALR外,突变≥3的患者与DIPSS-plus风险无关,与具有较少突变的患者相比,这些突变具有更高的移植后复发率和非复发死亡率。如DIPSS-plus所确定的,更高数量的突变的存在确定了在最高总体风险组中复发风险最高的患者。这些发现与未接受HCT的患者的分子风险分类是一致的,并支持结合突变信息的拟议移植风险分类。

更新日期:2020-03-16
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