Department of Laboratory Medicine; Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei.
Ann Oncol. 2011 Mar;22(3):696-704. doi: 10.1093/annonc/mdq402. Epub 2010 Aug 6.
The level of minimal residual disease (MRD) in acute myeloid leukemia (AML) at early time points (TPs) may be an important prognostic factor. Although internal tandem duplication of FLT3 (FLT3-ITD) as an MRD marker has been questioned for its instability based on semi-quantitative methods, we hypothesized that FLT3-ITD dynamics measured by sensitive quantitative real-time PCR at early TPs before appearance of instability may provide prognostic information.
We measured mutant quantity in 493 serial samples from 55 patients with a median follow-up time of 64.8 months. The FLT3-ITD quantities after induction (TP1) and after the first post-induction chemotherapy (TP2) were analyzed.
We found that lower FLT3-ITD levels at TP2 predicted longer overall survival (OS) and disease-free survival (DFS) regardless of cytogenetic risk. Multivariate analysis showed that ≥3 log reduction of FLT3-ITD at TP2 independently predicted better DFS and a trend toward better OS. FLT3-ITD disappeared at relapse in 16.7% of patients and none in those harboring mutant NPM1 compared with 29.4% in those with wild-type NPM1 (P = 0.032).
Though the mutation may disappear at relapse in a few patients, FLT3-ITD levels at early TPs after chemotherapy provide prognostic information. FLT3-ITD is significantly more stable in those with mutant NPM1.
急性髓系白血病（AML）早期时间点（TP）的微小残留病（MRD）水平可能是一个重要的预后因素。尽管基于半定量方法，FLT3 内部串联重复（FLT3-ITD）作为 MRD 标志物的不稳定性受到质疑，但我们假设在不稳定出现之前，通过早期 TP 的敏感定量实时 PCR 测量的 FLT3-ITD 动力学可能提供预后信息。
我们对 55 例患者的 493 个连续样本进行了检测，中位随访时间为 64.8 个月。分析了诱导后的突变量（TP1）和第一次诱导后化疗后的突变量（TP2）。
我们发现，TP2 时较低的 FLT3-ITD 水平与无论细胞遗传学风险如何，均与更长的总生存期（OS）和无病生存期（DFS）相关。多变量分析表明，TP2 时 FLT3-ITD 降低≥3 个对数独立预测更好的 DFS，且 OS 也有改善的趋势。在 16.7%的患者中，FLT3-ITD 在复发时消失，而在携带突变型 NPM1 的患者中无一例消失，而在野生型 NPM1 的患者中为 29.4%（P=0.032）。
尽管在少数患者中，突变可能在复发时消失，但化疗后早期 TP 的 FLT3-ITD 水平提供了预后信息。FLT3-ITD 在携带突变型 NPM1 的患者中更稳定。
