Division of Pediatric Oncology/Hematology, Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, Groningen, the Netherlands.
Haematologica. 2011 Sep;96(9):1310-7. doi: 10.3324/haematol.2011.040592. Epub 2011 May 23.
High white blood cell count at presentation is an unfavorable prognostic factor for treatment outcome in intermediate cytogenetic risk acute myeloid leukemia. Since the impact of white blood cell count on outcome of subgroups defined by the molecular markers NPMc(+) and FLT3-internal tandem duplication (ITD) is unknown, we addressed this issue.
We studied the effect of white blood cell count on outcome in a clinically and molecularly well-defined cohort of 525 patients with acute myeloid leukemia using these molecular markers. In addition, since an increased white blood cell count has been associated with an increased FLT3-ITD/FLT3 (wild-type) ratio, we investigated whether the effect of white blood cell count on outcome could be explained by the FLT3-ITD/FLT3 ratio.
This analysis revealed that white blood cell count had no impact on outcome in patients with the genotypic combinations 'NPMc(+) without FLT3-ITD' and 'NPM1 wild-type with or without FLT3-ITD'. In contrast, white blood cell count had a significant impact on complete remission rate (P=0.034), event-free survival (P=0.009) and overall survival (P<0.001) in patients with the genotypic combination 'NPMc(+) with FLT3-ITD'. A FLT3-ITD/FLT3 ratio greater than 1 was also associated with a reduced complete remission rate (P=0.066) and significantly reduced event-free survival (P= 0.001) and overall survival (P=0.001) in patients with the genotypic combination 'NPMc(+) with FLT3-ITD'. Multivariable analysis revealed that white blood cell count and FLT3-ITD/FLT3 ratio were independent prognostic indicators for outcome in the subgroup with the genotypic combination 'NPMc(+) with FLT3-ITD'.
Our results demonstrate that both high white blood cell count and FLT3-ITD/FLT3 ratio are prognostic factors in patients with acute myeloid leukemia with the genotypic combination 'NPMc(+) with FLT3-ITD'.
高白细胞计数是中危细胞遗传学急性髓系白血病治疗结果的不利预后因素。由于白细胞计数对 NPMc(+)和 FLT3 内部串联重复（ITD）等分子标志物定义的亚组结果的影响尚不清楚，我们对此进行了研究。
我们使用这些分子标志物研究了 525 例急性髓系白血病患者的临床和分子特征明确的队列中白细胞计数对结果的影响。此外，由于白细胞计数升高与 FLT3-ITD/FLT3（野生型）比值升高相关，我们研究了白细胞计数对结果的影响是否可以通过 FLT3-ITD/FLT3 比值来解释。
该分析显示，白细胞计数对基因型组合“NPMc(+)无 FLT3-ITD”和“NPM1 野生型伴或不伴 FLT3-ITD”的患者的结果无影响。相反，白细胞计数对基因型组合“NPMc(+)伴 FLT3-ITD”的患者的完全缓解率（P=0.034）、无事件生存率（P=0.009）和总生存率（P<0.001）有显著影响。FLT3-ITD/FLT3 比值大于 1 也与基因型组合“NPMc(+)伴 FLT3-ITD”患者的完全缓解率降低（P=0.066）以及无事件生存率（P=0.001）和总生存率（P=0.001）显著降低相关。多变量分析显示，白细胞计数和 FLT3-ITD/FLT3 比值是基因型组合“NPMc(+)伴 FLT3-ITD”患者预后的独立预后因素。
我们的结果表明，高白细胞计数和 FLT3-ITD/FLT3 比值均是基因型组合“NPMc(+)伴 FLT3-ITD”的急性髓系白血病患者的预后因素。
