Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation.
Impact of IDH1 and IDH2 mutational subgroups in AML patients after allogeneic stem cell transplantation.
复制标题
DOI：
10.1186/s13045-022-01339-8
复制
发表时间：
2022-09-05
影响因子：
28.5
通讯作者：
Stoelzel, Friedrich
中科院分区：
文献类型：
--
作者：
Kunadt, Desiree;Stasik, Sebastian;Metzeler, Klaus H.;Roellig, Christoph;Schliemann, Christoph;Greif, Philipp A.;Spiekermann, Karsten;Rothenberg-Thurley, Maja;Krug, Utz;Braess, Jan;Kraemer, Alwin;Hochhaus, Andreas;Scholl, Sebastian;Hilgendorf, Inken;Bruemmendorf, Tim H.;Jost, Edgar;Steffen, Bjoern;Bug, Gesine;Einsele, Hermann;Goerlich, Dennis;Sauerland, Cristina;Schaefer-Eckart, Kerstin;Krause, Stefan W.;Haenel, Mathias;Hanoun, Maher;Kaufmann, Martin;Woermann, Bernhard;Kramer, Michael;Sockel, Katja;Egger-Heidrich, Katharina;Herold, Tobias;Ehninger, Gerhard;Burchert, Andreas;Platzbecker, Uwe;Berdel, Wolfgang E.;Mueller-Tidow, Carsten;Hiddemann, Wolfgang;Serve, Hubert;Stelljes, Matthias;Baldus, Claudia D.;Neubauer, Andreas;Schetelig, Johannes;Thiede, Christian;Bornhaeuser, Martin;Middeke, Jan M.;Stoelzel, Friedrich
异基因造血细胞移植 (alloHCT) 在 IDH1/2 突变的急性髓系白血病 (AML) 中的作用尚未明确。因此，我们分析了 3234 名接受 alloHCT 或传统化疗巩固的首次完全缓解 (CR1) AML 患者的大型队列，并研究了 IDH1/2 突变亚组（IDH1 R132C、R132H 和 IDH2 R140Q、R172K）的结果。在诊断时从骨髓或外周血样本中提取基因组 DNA，并分别通过变性高效液相色谱、桑格测序和靶向骨髓组新一代测序来分析 IDH 突变。使用 R 和标准统计方法（连续变量的 Kruskal-Wallis 检验、分类变量的卡方检验、单变量和多变量模型的 Cox 回归）进行统计处理分析，将 alloHCT 作为时间依赖性协变量。在 3234 名达到 CR1 的患者中，7.8% 携带 IDH1 突变（36% R132C 和 47% R132H），10.9% 携带 IDH2 突变（77% R140Q 和 19% R172K）。 852 名 CR1 患者接受了 alloHCT。在 alloHCT 组中，6.2% 的患者存在 IDH1 突变（43.4% R132C 和 41.4% R132H），10% 的患者存在 IDH2 突变（71.8% R140Q 和 24.7% R172K）。与仅化疗相比，IDH1 R132C 和 IDH2 R172K 变体显示 alloHCT 对 OS（p = .017 和 p = .049）和 RFS（HR = 0.42、p = .048 和 p = .009）具有显着益处。 IDH2 R140Q 突变 AML 中的 AlloHCT 导致 RFS 更长（HR = 0.4，p = .002）。在这项大型治疗分析中，我们表明alloHCT能够克服一线巩固治疗中某些IDH突变亚类的负面预后影响，并且可以等待预后验证，为AML风险分层和治疗决策提供预后价值。在线版本包含可在 10.1186/s13045-022-01339-8 获取的补充材料。
The role of allogeneic hematopoietic cell transplantation (alloHCT) in acute myeloid leukemia (AML) with mutated IDH1/2 has not been defined. Therefore, we analyzed a large cohort of 3234 AML patients in first complete remission (CR1) undergoing alloHCT or conventional chemo-consolidation and investigated outcome in respect to IDH1/2 mutational subgroups (IDH1 R132C, R132H and IDH2 R140Q, R172K). Genomic DNA was extracted from bone marrow or peripheral blood samples at diagnosis and analyzed for IDH mutations with denaturing high-performance liquid chromatography, Sanger sequencing and targeted myeloid panel next-generation sequencing, respectively. Statistical as-treated analyses were performed using R and standard statistical methods (Kruskal–Wallis test for continuous variables, Chi-square test for categorical variables, Cox regression for univariate and multivariable models), incorporating alloHCT as a time-dependent covariate. Among 3234 patients achieving CR1, 7.8% harbored IDH1 mutations (36% R132C and 47% R132H) and 10.9% carried IDH2 mutations (77% R140Q and 19% R172K). 852 patients underwent alloHCT in CR1. Within the alloHCT group, 6.2% had an IDH1 mutation (43.4% R132C and 41.4% R132H) and 10% were characterized by an IDH2 mutation (71.8% R140Q and 24.7% R172K). Variants IDH1 R132C and IDH2 R172K showed a significant benefit from alloHCT for OS (p = .017 and p = .049) and RFS (HR = 0.42, p = .048 and p = .009) compared with chemotherapy only. AlloHCT in IDH2 R140Q mutated AML resulted in longer RFS (HR = 0.4, p = .002). In this large as-treated analysis, we showed that alloHCT is able to overcome the negative prognostic impact of certain IDH mutational subclasses in first-line consolidation treatment and could pending prognostic validation, provide prognostic value for AML risk stratification and therapeutic decision making. The online version contains supplementary material available at 10.1186/s13045-022-01339-8.
登录
查看更多内容
影响因子：
11.4
作者：
Braess J;Amler S;Kreuzer KA;Spiekermann K;Lindemann HW;Lengfelder E;Graeven U;Staib P;Ludwig WD;Biersack H;Ko YD;Uppenkamp MJ;De Wit M;Korsten S;Peceny R;Gaska T;Schiel X;Behringer DM;Kiehl MG;Zinngrebe B;Meckenstock G;Roemer E;Medgenberg D;Spaeth-Schwalbe E;Massenkeil G;Hindahl H;Schwerdtfeger R;Trenn G;Sauerland C;Koch R;Lablans M;Faldum A;Görlich D;Bohlander SK;Schneider S;Dufour A;Buske C;Fiegl M;Subklewe M;Braess B;Unterhalt M;Baumgartner A;Wörmann B;Beelen D;Hiddemann W;AML-CG
通讯作者：
AML-CG
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：
Chou, W-C;Lei, W-C;Tien, H-F
通讯作者：
Tien, H-F
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：
28.5
作者：
Chotirat S;Thongnoppakhun W;Promsuwicha O;Boonthimat C;Auewarakul CU
通讯作者：
Auewarakul CU