Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.
Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.
J Hematol Oncol. 2022 Sep 5;15(1):126. doi: 10.1186/s13045-022-01339-8.
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.
异基因造血细胞移植（alloHCT）在伴有突变 IDH1/2 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 例在首次完全缓解（CR1）期接受 alloHCT 或常规化疗巩固治疗的 AML 患者的大型队列，并根据 IDH1/2 突变亚组（IDH1 R132C、R132H 和 IDH2 R140Q、R172K）研究了预后。
从骨髓或外周血样本中提取基因组 DNA，分别采用变性高效液相色谱法、Sanger 测序和靶向髓系 panel 下一代测序分析 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）进行基于治疗的统计分析，将 alloHCT 作为时变协变量。
在 3234 例达到 CR1 的患者中，7.8%存在 IDH1 突变（36%为 R132C，47%为 R132H），10.9%存在 IDH2 突变（77%为 R140Q，19%为 R172K）。852 例患者在 CR1 期接受 alloHCT。在 alloHCT 组中，6.2%存在 IDH1 突变（43.4%为 R132C，41.4%为 R132H），10%存在 IDH2 突变（71.8%为 R140Q，24.7%为 R172K）。IDH1 R132C 和 IDH2 R172K 突变与仅接受化疗相比， alloHCT 对 OS（p=0.017 和 p=0.049）和 RFS（HR=0.42，p=0.048 和 p=0.009）有显著获益。alloHCT 可改善 IDH2 R140Q 突变 AML 的 RFS（HR=0.4，p=0.002）。
在这项大型基于治疗的分析中，我们表明 alloHCT 能够克服一线巩固治疗中某些 IDH 突变亚组的不良预后影响，并可能在预后验证后，为 AML 风险分层和治疗决策提供预后价值。
