Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation.
Impact of IDH1 and IDH2 mutation detection at diagnosis and in remission in patients with AML receiving allogeneic transplantation.
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DOI：
10.1182/bloodadvances.2021005789
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发表时间：
2023-02-14
期刊：
影响因子：
7.5
通讯作者：
Schwind, Sebastian
中科院分区：
文献类型：
--
作者：
Bill, Marius;Jentzsch, Madlen;Bischof, Lara;Kohlschmidt, Jessica;Grimm, Juliane;Schmalbrock, Laura Katharina;Backhaus, Donata;Brauer, Dominic;Goldmann, Karoline;Franke, Georg -Nikolaus;Vucinic, Vladan;Niederwieser, Dietger;Mims, Alice S.;Platzbecker, Uwe;Eisfeld, Ann-Kathrin;Schwind, Sebastian
AML中IDH突变的诊断状态并不显著影响HSCT后的预后。HSCT中IDH1R132和IDH2R172阳性的MRD与预后不良相关。异柠檬酸脱氢酶1和2基因(IDH1和IDH2)的体细胞突变在急性髓系白血病(AML)中很常见。IDH突变的存在对预后的影响可能受到突变状态、诊断时突变的特定位置(即IDH1 R132、IDH2 R140和IDH2 R172)以及病程中突变负担的动态变化的影响。尽管许多IDH突变的AML患者通过造血干细胞移植(HSCT)得到巩固，但其潜在的生物学和预后后果在很大程度上仍然未知。在这里，我们对292例AML患者进行了大规模的分析，这些患者接受了完全缓解(CR)或CR伴不完全外周恢复(CRI)的HSCT，其中我们在诊断时评估了IDH突变状态，并将HSCT作为可测量残留病(MRD)的潜在标记物。大约四分之一的患者在确诊时发生了等位基因突变。AML中IDH突变的诊断存在与HSCT合并时并不具有显著的预后影响。然而，IDH1 R132和IDH2 R172在HSCT缓解期MRD阳性与复发风险增加相关，而IDH2 R140突变与复发风险无关。诊断时IDH2R140变异等位基因频率(VAF)较高，聚集率在50%左右，形态缓解期HSCT的突变清除率明显低于IDH1R132和IDH2R172。在我们的队列中，IDH2 R140突变表现得更像是一种克隆性造血相关的异常，而IDH1 R132和IDH2 R172则具有AML疾病特有的特征。
The diagnostic IDH mutation status in AML did not significantly influence outcomes following HSCT. IDH1 R132 and IDH2 R172 positive MRD at HSCT is associated with inferior outcomes. Somatic mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) are common in acute myeloid leukemia (AML). The prognostic impact of the presence of IDH mutations may be influenced by the comutational status, the specific location of the mutation (ie, IDH1 R132, IDH2 R140, and IDH2 R172) at diagnosis, and the dynamics of the mutation burden during disease course. Even though many patients with IDH-mutated AML are consolidated by hematopoietic stem cell transplantation (HSCT), the underlying biology and prognostic consequences remain largely unknown. Here, we present a large analysis of 292 patients with AML who received HSCT in complete remission (CR) or CR with incomplete peripheral recovery (CRi), in which we assessed the IDH mutation status at diagnosis and HSCT as a potential marker for measurable residual disease (MRD). About a quarter of all patients were IDH-mutated at diagnosis. The diagnostic presence of IDH mutations in AML did not have a significant prognostic impact when consolidated with HSCT. However, IDH1 R132 and IDH2 R172 MRD positivity in remission at HSCT associated with an increased risk of relapse, while IDH2 R140 mutations did not. The IDH2 R140 variant allele frequency (VAF) at diagnosis was higher, clustering around 50%, and the mutation clearance at HSCT in morphologic remission was much lower compared with IDH1 R132 and IDH2 R172. In our cohort, IDH2 R140 mutations behaved more like a clonal hematopoiesis-related aberration, while IDH1 R132 and IDH2 R172 harbored AML disease-specific features.
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影响因子：
64.8
作者：
Lu, Chao;Ward, Patrick S.;Kapoor, Gurpreet S.;Rohle, Dan;Turcan, Sevin;Abdel-Wahab, Omar;Edwards, Christopher R.;Khanin, Raya;Figueroa, Maria E.;Melnick, Ari;Wellen, Kathryn E.;O'Rourke, Donald M.;Berger, Shelley L.;Chan, Timothy A.;Levine, Ross L.;Mellinghoff, Ingo K.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
50.3
作者：
Figueroa ME;Abdel-Wahab O;Lu C;Ward PS;Patel J;Shih A;Li Y;Bhagwat N;Vasanthakumar A;Fernandez HF;Tallman MS;Sun Z;Wolniak K;Peeters JK;Liu W;Choe SE;Fantin VR;Paietta E;Löwenberg B;Licht JD;Godley LA;Delwel R;Valk PJ;Thompson CB;Levine RL;Melnick A
通讯作者：
Melnick A
影响因子：
11.4
作者：
Meggendorfer, Manja;Cappelli, Luca Vincenzo;Haferlach, Torsten
通讯作者：
Haferlach, Torsten
影响因子：
158.5
作者：
DiNardo, C. D.;Stein, E. M.;Kantarjian, H. M.
通讯作者：
Kantarjian, H. M.
影响因子：
20.3
作者：
Gupta, Vikas;Tallman, Martin S.;Weisdorf, Daniel J.
通讯作者：
Weisdorf, Daniel J.