Department of Laboratory Hematology, University Health Network, Toronto, Ontario, Canada M5G 2C4; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada M5S 1A1.
Hum Pathol. 2013 Oct;44(10):2038-46. doi: 10.1016/j.humpath.2013.03.007. Epub 2013 May 21.
Patients with acute myeloid leukemia (AML) harboring an NPM1 mutation exhibit a heterogeneous clinical outcome. Recent studies have shown that the absence of FLT3 internal tandem duplication (FLT3-ITD) mutation confers a favorable prognosis in NPM1-positive AML. However, the prognostic impact of immunophenotypes in this subgroup remains unclear. In this study, FLT3 mutation status and immunophenotypic profile of 85 NPM1-positive patients with de novo AML were retrospectively analyzed and correlated with their clinical features and survival outcomes. Univariate analysis detected 5 markers with prognostic relevance: older age (≥60 years), high white blood cell (WBC) count (>30 × 10(9)/L), FLT3-ITD, CD7, and CD34 expression. Multivariate analysis showed that high WBC count was the only independent predictor of a lower complete remission rate (P = .019). Older age (P = .035), high WBC count (P = .008), FLT3-ITD (P = .012), and CD34 expression (P = .006) were independent predictors of a shorter event-free survival (EFS). High WBC count (P = .014), FLT3-ITD (P = .005), and CD34 expression (P = .047) were independent predictors of a shorter overall survival (OS). Furthermore, based on FLT3-ITD status in NPM1 mutation-positive patients, we showed that both high WBC and CD34 expression conferred a poor EFS (P = .010 and P = .016, respectively) and OS (P = .032 and P = .001, respectively) in the FLT3-ITD-negative group, whereas high WBC predicted a poor EFS (P = .016) and OS (P = .027) in the FLT3-ITD-positive group. Our results confirm the prognostic value of assessing FLT3-ITD mutations in NPM1-positive AML and identify the adverse prognostic impact of high WBC and CD34 expression in this subgroup of AML.
患有伴 NPM1 突变的急性髓系白血病(AML)的患者具有不同的临床结局。最近的研究表明,无 FLT3 内部串联重复(FLT3-ITD)突变的情况下,NPM1 阳性 AML 预后较好。然而,该亚组中的免疫表型的预后影响仍不清楚。在这项研究中,回顾性分析了 85 例初诊 AML 伴 NPM1 阳性患者的 FLT3 突变状态和免疫表型特征,并将其与临床特征和生存结果相关联。单因素分析检测到 5 个具有预后相关性的标志物:年龄较大(≥60 岁)、白细胞(WBC)计数较高(>30×10(9)/L)、FLT3-ITD、CD7 和 CD34 表达。多因素分析表明,高 WBC 计数是完全缓解率较低的唯一独立预测因素(P=.019)。年龄较大(P=.035)、高 WBC 计数(P=.008)、FLT3-ITD(P=.012)和 CD34 表达(P=.006)是无事件生存(EFS)较短的独立预测因素。高 WBC 计数(P=.014)、FLT3-ITD(P=.005)和 CD34 表达(P=.047)是总生存(OS)较短的独立预测因素。此外,根据 NPM1 突变阳性患者的 FLT3-ITD 状态,我们发现高 WBC 和 CD34 表达在 FLT3-ITD 阴性组中均预示着较差的 EFS(P=.010 和 P=.016)和 OS(P=.032 和 P=.001),而高 WBC 在 FLT3-ITD 阳性组中预示着较差的 EFS(P=.016)和 OS(P=.027)。我们的结果证实了评估 NPM1 阳性 AML 中 FLT3-ITD 突变的预后价值,并确定了该亚组中高 WBC 和 CD34 表达的不良预后影响。