Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany.
Blood. 2011 Apr 28;117(17):4561-8. doi: 10.1182/blood-2010-08-303479. Epub 2011 Mar 3.
To integrate available clinical and molecular information for cytogenetically normal acute myeloid leukemia (CN-AML) patients into one risk score, 275 CN-AML patients from multicenter treatment trials AML SHG Hannover 0199 and 0295 and 131 patients from HOVON/SAKK protocols as external controls were evaluated for mutations/polymorphisms in NPM1, FLT3, CEBPA, MLL, NRAS, IDH1/2, and WT1. Transcript levels were quantified for BAALC, ERG, EVI1, ID1, MN1, PRAME, and WT1. Integrative prognostic risk score (IPRS) was modeled in 181 patients based on age, white blood cell count, mutation status of NPM1, FLT3-ITD, CEBPA, single nucleotide polymorphism rs16754, and expression levels of BAALC, ERG, MN1, and WT1 to represent low, intermediate, and high risk of death. Complete remission (P = .005), relapse-free survival (RFS, P < .001), and overall survival (OS, P < .001) were significantly different for the 3 risk groups. In 2 independent validation cohorts of 94 and 131 patients, the IPRS predicted different OS (P < .001) and RFS (P < .001). High-risk patients with related donors had longer OS (P = .016) and RFS (P = .026) compared with patients without related donors. In contrast, intermediate-risk group patients with related donors had shorter OS (P = .003) and RFS (P = .05). Donor availability had no impact on outcome of patients in the low-risk group. Thus, the IPRS may improve consolidation treatment stratification in CN-AML patients. Study registered at www.clinicaltrials.gov as #NCT00209833.
为了将现有的临床和分子信息整合到细胞遗传学正常的急性髓细胞白血病（CN-AML）患者的一个风险评分中，对来自多中心治疗试验 AML SHG Hannover 0199 和 0295 的 275 例 CN-AML 患者和 HOVON/SAKK 方案的 131 例患者进行了评估，评估内容包括 NPM1、FLT3、CEBPA、MLL、NRAS、IDH1/2 和 WT1 的突变/多态性。还定量分析了 BAALC、ERG、EVI1、ID1、MN1、PRAME 和 WT1 的转录水平。根据年龄、白细胞计数、NPM1、FLT3-ITD、CEBPA、单核苷酸多态性 rs16754 突变状态以及 BAALC、ERG、MN1 和 WT1 的表达水平，在 181 例患者中建立了综合预后风险评分（IPRS），以代表死亡的低、中、高风险。3 个风险组的完全缓解率（P =.005）、无复发生存率（RFS，P <.001）和总生存率（OS，P <.001）均有显著差异。在 94 例和 131 例患者的 2 个独立验证队列中，IPRS 预测了不同的 OS（P <.001）和 RFS（P <.001）。与无供者的患者相比，高危患者有相关供者时 OS（P =.016）和 RFS（P =.026）更长。相比之下，中危组患者有相关供者时 OS（P =.003）和 RFS（P =.05）更短。供者的可用性对低危组患者的结果没有影响。因此，IPRS 可能改善 CN-AML 患者的巩固治疗分层。该研究在 www.clinicaltrials.gov 上注册，编号为 #NCT00209833。
