Gui Gege, Ravindra Niveditha, Hegde Pranay S, Andrew Georgia, Mukherjee Devdeep, Wong Zoë, Auletta Jeffery J, El Chaer Firas, Chen Evan C, Chen Yi-Bin, Corner Adam, Devine Steven M, Iyer Sunil G, Jimenez Jimenez Antonio Martin, De Lima Marcos J G, Litzow Mark R, Kebriaei Partow, Saber Wael, Spellman Stephen R, Zeger Scott L, Page Kristin M, Dillon Laura W, Hourigan Christopher S
Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Bone Marrow Transplant. 2025 Feb;60(2):144-153. doi: 10.1038/s41409-024-02449-2. Epub 2024 Oct 25.
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.
急性髓系白血病（AML）初诊时的常规基因分析有助于进行亚组特异性预后评估、药物研发及临床管理策略制定。然而，AML亚组治疗反应评估的最佳方法尚未确定。2013年至2019年期间，美国一个全国性队列纳入了257例处于首次缓解期（CR1）、伴有异柠檬酸脱氢酶2突变（IDH2m）的成年AML患者，这些患者接受了异基因移植，移植后三年的复发率和生存率分别为24%和71%。移植前的临床流式细胞术评估在根据移植后复发或死亡风险对患者进行分层方面并无用处。对移植前100天内采集的CR1期血液进行DNA测序。持续检测到IDH2m很常见（51%），与检测呈阴性相比，复发和死亡风险增加。在该队列中，初诊时与NPM1突变和/或FLT3-ITD共突变很常见（41%），与IDH2m检测相比，使用这些经过验证的微小残留病（MRD）标志物能提供更好的分层。移植前IDH2m检测呈阴性的患者复发相关死亡率较低，无论预处理强度如何。2017年8月美国食品药品监督管理局（FDA）批准恩杂鲁胺后，移植前缓解期持续检测到IDH2m的患者移植后复发率降低。
