初诊急性髓系白血病合并骨髓纤维化患者的临床特征、基因突变及预后分析

Analysis of clinical features,gene mutation,and prognostic characteristics in de novo acute myeloid leukemia patients with myelofibrosis

目的探讨初诊急性髓系白血病(AML)合并骨髓纤维化(MF)患者的基因突变、临床及预后特征。方法2016年1月1日至2020年2月1日河南省人民医院收治的初诊并同时行骨髓活组织检查的103例AML患者纳入研究,根据WHO(2016)骨髓纤维化分级标准将患者分为AML伴MF组(MF-1~3)与AML不伴MF组(MF-0),并对两组患者的临床特征、基因突变、疗效和预后进行回顾性比较。结果①103例患者中AML伴MF组46例(44.7%),其中MF-139例(84.8%),MF-2/37例(15.2%);AML不伴MF组57例(55.3%)。和AML不伴MF组相比,AML伴MF组中位WBC显著增高[11.205(0.69~191.82)×10^9/L对4.64(0.18~95.10)×10^9/L,P=0.024];外周血出现有核红细胞的比例明显增高(43.5%对24.6%,χ^2=4.119,P=0.042);FAB分型:4例AML-M0患者均在AML伴MF组,而AML不伴MF组AML-M2所占比例更高(P=0.014)。②AML伴MF组患者FLT3-ITD及NPM1基因突变率更高(15.2%对1.8%,P=0.021;26.1%对10.5%,P=0.039),而CEBPA基因突变率明显低于AML不伴MF组(2.2%对17.5%,P=0.029)。③AML伴MF组完全缓解(CR)率显著低于AML不伴MF组(69.7%对93.2%,χ^2=7.412,P=0.006)。多因素分析显示MF,尤其是纤维化程度是影响初诊AML患者CR的独立危险因素。④AML伴MF组3年总生存(OS)率明显低于AML不伴MF组(20.5%对72.2%,χ^2=4.032,P=0.045);亚组分析显示MF-1和MF-2/3两组患者的OS率、无进展生存(PFS)率显著低于AML不伴MF组(P=0.001)。Cox多因素分析显示MF,尤其是MF-2/3是影响初诊AML患者OS和PFS的独立危险因素(P值分别为0.021和0.044)。结论AML合并MF患者具有较为独特的实验室及临床特征;MF是影响AML患者CR、OS和PFS的独立预后不良指标,MF的评估对初诊AML的疗效和预后判断具有重要意义。

Objective This study aims to investigate the characteristics of gene mutation and clinical prognosis in de novo acute myeloid leukemia(AML)patients with myelofibrosis(MF).Methods From January 1,2016,to February 1,2020,103 newly diagnosed AML patients in Henan Provincial People’s Hospital who simultaneously underwent bone marrow biopsy examination were included.They were divided into the AML-MF group(MF grades 1-3)and the AML without MF group(MF grade 0),and the clinical features,gene alterations,chemotherapy efficacy,and prognosis were compared between the two groups retrospectively.Results①MF was confirmed in 44.7%of AML patients(46/103),of which 84.8%(39/46)were MF-1 and 15.2%(7/46)were MF-2/3,while MF was not confirmed in 55.3%(57/103)of AML patients.The median of WBC in the AML-MF group was significantly higher than in the AML without MF group[11.205(0.69-191.82)×10^9/L vs 4.64(0.18-95.10)×10^9/L,P=0.024].More patients in the AML-MF group had nucleated erythrocytes in the peripheral blood(43.5%vs 24.6%,χ^2=4.119,P=0.042).All four AML-M0 patients were in the AML-MF group,while AML without MF group had a higher proportion of AML-M2(P=0.014).②FLT3-ITD and NPM1 mutations were more frequent in the AML-MF group(P=0.021 and 0.039),while CEBPA mutation was more frequent in the AML without MF group(P=0.029).③The CR rate in the AML-MF group was significantly lower than in the AML without MF group(69.7%vs 93.2%)(χ^2=7.412,P=0.006).Multivariate analysis showed that MF,especially the grade of fibrosis,was an independent risk factor for CR in de novo AML.④The 3-year OS of patients in the AML-MF group was significantly lower than in the AML without MF group(20.5%vs 72.2%,χ^2=4.032,P=0.045).Subgroup analysis showed that OS and PFS of AML-MF1 and AML-MF 2/3 groups were also significantly worse than those of the AML without MF group(P=0.001)and MF,especially MF≥2,was an independent marker for inferior OS and PFS in de novo AML(P=0.021 and 0.044).Conclusion AML-MF has unique laboratory and clinical characteristics.MF is an independent risk factor for CR,OS,and PFS in AML.Evaluation of MF is very significant for therapy efficacy and prognosis judgment in de novo AML.