摘要
目的:探讨FLT3-ITD突变高等位基因比率在急性髓系白血病(AML)患者中的预后意义。方法:筛选100例检测到FLT3-ITD等位基因比率的AML初诊患者的临床资料,对其临床特征及预后因素进行统计学分析。结果:100例患者初诊时中位白细胞计数为80.1×10^(9)/L(2×109/L~326×10^(9)/L),中位骨髓原始细胞比例数为68.5%(21%~95%),细胞遗传学检查示正常核型66例。将FLT3-ITD等位基因比率阈值设置在1.0,分为低等位基因比率组(<1.0,64例)和高等位基因比率组(≥1.0,36例)进行分析,这些患者的初次完全缓解(CR1)率总体为70.0%,低等位基因比率组和高等位基因比率组间CR1率差异有统计学意义(82.8%vs 47.2%,P<0.001)。在接受异基因造血干细胞移植(allo-HSCT)的65例患者中,低等位基因比率组的无复发生存(RFS)和总生存(OS)明显优于高等位基因比率组(RFS:P=0.007,OS:P=0.014)。而对于高等位基因比率组患者,allo-HSCT与化疗比较,未能明显改善其RFS及OS(RFS:P=0.539,OS:P=0.579)。在未进行allo-HSCT的患者中,低等位基因比率组和高等位基因比率组间RFS和OS差异无统计学意义(RFS:P=0.538,OS:P=0.854)。伴有其他突变(CEBPA、NPM1、DNMT3A)的FLT3-ITD高等位基因比率患者的CR1、OS、RFS,与低等位基因比率患者比较差异无统计学意义(P>0.05)。对患者的预后因素进行分析发现,CR1、外周白细胞计数及allo-HSCT在单因素、多因素分析中均对RFS、OS有影响。FLT3-ITD高等位基因比率的AML患者能检测到13号染色体长臂杂合性丢失(LOH),且等位基因比率值越高,LOH检测到的频率越高。结论:FLT3-ITD突变高等位基因比率的AML患者具有较高的白细胞计数,多合并NPM1突变、CR1率低及OS、RFS短的特征。对于不同化疗效果均差,即使进行allo-HSCT也未能明显改善其OS及RFS。高等位基因比率患者存在LOH状态,等位基因比率值越高,LOH频率越高。
Objective:To investigate the prognostic impact of high allelic ratio(AR)of FLT3-ITD mutation in patients with acute myeloid leukemia(AML).Methods:The clinical characteristics and prognostic factors of 100 AML patients with FLT3-ITD AR were analyzed.Results:The median white blood cell counts and bone marrow blasts at initial diagnosis of 100 patients were 80.1×10^(9)/L(2×10^(9)/L to 326×10^(9)/L)and 68.5%(21%to 95%),respectively.Cytogenetic analysis showed normal karyotype in 66 cases.These patients were separated into high AR(≥1.0,36 cases)and low AR(<1.0,64 cases)according to the cut-off values for FLT3-ITD AR at 1.0.The overall success rate of the first complete remission(CR1)was 70.0%,and there was no significant difference in CR1 rate between the low AR and high AR groups(82.8%vs 47.2%,P<0.001).In 65 patients receiving allo-HSCT,the low AR group had a significantly superior outcome in RFS and OS than the high AR group(RFS:P=0.007,OS:P=0.014).However,allo-HSCT failed to improve RFS and OS in patients with high AR group(RFS:P=0.539,OS:P=0.579).In the group which allo-HSCT was not performed,there was no significant difference in RFS and OS between the low AR and high AR groups(RFS:P=0.538,OS:P=0.854).Also,there was no significant difference between CR1,OS,and RFS in FLT3-ITD patients of high AR with other mutations(CEBPA,NPM1,DNMT3 A)(P>0.05).CR1,peripheral leukocyte count and allo-HSCT influenced the RFS and OS of these patients in univariate and multivariate analysis.FLT3-ITD patients with high AR could detect loss of heterozygosity(LOH)of chromosome 13 q,and the higher the AR value,the higher the frequency of LOH detection.Conclusion:Patients with high AR of FLT3-ITD mutation in AML have higher white blood cell counts,commonly associated with NPM1 mutations,low CR1,and short OS and RFS.Allo-HSCT also failed to significantly improve OS and RFS in patients with high AR group.Patients with high AR have LOH status.The higher the AR value,the higher the LOH frequency.
作者
蔡颖
陈苏宁
沈宏杰
文丽君
杨小飞
许小宇
CAI Ying;CHEN Suning;SHEN Hongjie;WEN Lijun;YANG Xiaofei;XU Xiaoyu(Department of Hematology,Jiangyin Peoples Hospital,Jiangyin,214400,China;The First Affiliated Hospital of Soochow University,Jiangsu Institute of Hematology)
出处
《临床血液学杂志》
CAS
2021年第5期319-326,共8页
Journal of Clinical Hematology
基金
国家自然科学基金(No:81570139)。
