急性髓性白血病异基因移植前可测量的残留突变 IDH2。

IF 4.5 2区 医学 Q1 HEMATOLOGY
Gege Gui, Niveditha Ravindra, Pranay S Hegde, Georgia Andrew, Devdeep Mukherjee, Zoë Wong, Jeffery J Auletta, Firas El Chaer, Evan C Chen, Yi-Bin Chen, Adam Corner, Steven M Devine, Sunil G Iyer, Antonio Martin Jimenez Jimenez, Marcos J G De Lima, Mark R Litzow, Partow Kebriaei, Wael Saber, Stephen R Spellman, Scott L Zeger, Kristin M Page, Laura W Dillon, Christopher S Hourigan
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引用次数: 0

摘要

对急性髓性白血病(AML)进行初步诊断时的常规基因分析,有助于针对亚组的预后、药物开发和临床管理策略。然而,急性髓细胞白血病亚组治疗反应评估的最佳方法尚未确定。2013-2019年期间,美国对257名首次缓解(CR1)的伴有IDH2突变(IDH2m)的急性髓细胞性白血病成年患者进行了异基因移植,移植后三年的复发率和存活率分别为24%和71%。移植前临床流式细胞术评估无法根据移植后复发或死亡风险对患者进行分层。对移植前100天内采集的CR1血液进行了DNA测序。持续检测到IDH2m的情况很常见(51%),与检测结果为阴性的患者相比,IDH2m检测结果与复发和死亡的增加有关。与IDH2m检测相比,使用这些经过验证的MRD标记物能提供更好的分层。移植前IDH2m检测阴性的患者复发相关死亡率较低,与调理强度无关。2017年8月FDA批准依那西尼后,移植前缓解期持续检测到IDH2m的患者移植后复发率较低。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Measurable residual mutated IDH2 before allogeneic transplant for acute myeloid leukemia.

Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017.

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来源期刊
Bone Marrow Transplantation
Bone Marrow Transplantation 医学-免疫学
CiteScore
8.40
自引率
8.30%
发文量
337
审稿时长
6 months
期刊介绍: Bone Marrow Transplantation publishes high quality, peer reviewed original research that addresses all aspects of basic biology and clinical use of haemopoietic stem cell transplantation. The broad scope of the journal thus encompasses topics such as stem cell biology, e.g., kinetics and cytokine control, transplantation immunology e.g., HLA and matching techniques, translational research, and clinical results of specific transplant protocols. Bone Marrow Transplantation publishes 24 issues a year.
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