摘要
目的:探讨FLT3-ITD基因及其碱基重排长度对急性髓系白血病(AML)患者总体生存时间(OS)及无复发生存时间(RFS)的影响。方法:回顾分析2011年6月至2016年4月收治的75例FLT3-ITD^+ AML(除外M3)及76例FLT3-ITD^-正常核型AML(除外M3,作为对照组)患者临床资料;采用DNA基因测序分析40例FLT3-ITD^+ AML患者ITD基因重排碱基长度。结果:FLT3-ITD^+ AML患者初诊时白细胞数、骨髓原始细胞比例较FLT3-ITD^- AML患者高(95.13 vs 10.85(P<0.01);72%vs 59%,P=0.003),CR率较FLT3-ITD^-患者低(70.42%vs 94.7%(P<0.01)。接受造血干细胞移植的FLT3-ITD^+患者OS及RFS明显长于单纯化疗FLT3-ITD^+患者(P<0.01),且移植后早期接受索拉菲尼维持治疗患者OS和RFS较未接受者明显延长(P<0.05和P<0.05)。FLT3-ITD插入重排碱基长度<60 bp组OS长于≥60 bp(P<0.05),其中2组单纯化疗患者OS及RFS差异无统计学意义。而在接受异基因造血干细胞移植患者中,重排碱基长度<60 bp组OS长于≥60 bp组(中位OS分别未达到、达到、15个月,P<0.05),且与allo-HSCT FLT3-ITD^-患者OS相似。结论:FIT3-ITD^+ AML患者(除外M3)预后较FLT3-ITD^-患者差,其中ITD重排碱基长度≥60 bp患者预后更差,单纯化疗并不能改善FLT3-ITD^+患者的预后。造血干细胞移植能够明显延长RFS,移植后早期索拉菲尼维持治疗能显著改善这类患者的预后。
Objective： To explore the influence of FLT3-ITD mutation and ITD length on the overall survival（ OS） and relapse free survival（ RFS） in patients with non-M3 acute myeloid leukemia.Methods： Clinical features and therapeutic effect were retrospectively analyzed in 75 AML patients with FLT3-ITD mutation and 76 FLT3-ITD-AML patients with a normal karotype from June 2011 to April 2016.Genomic DNA was amplified by PCR,and FLT3-ITD mutation length was analyzed by DNA sequencing in 40 patients.Results： AML patients with FLT3-ITD mutation had higher WBC count and the ratio of BMblast cells at initial diagnosis was also higher than those in AML patients without FLT3-ITD mutation（95.13 vs 10.85）（P〈0.01）;72% vs 59%（P〈0.01）.The CR rates in AML patients with FLT3-ITD mutation less than those in AML patients without FLT3-ITD mutation（70.42% vs 94.7%）（ P〈0.01）.OS（ P〈0.01） and RFS（ P〈0.01）were significantly increased in patients with AML who received allo-HSCT as compared with the patients who received consolidation chemotherapy and similar to AML patients without FLT3-ITD mutation who received HSCT.Patients with maintenance sorafenib after HSCT had longer OS（ P〈0.05） and RFS（ P〈0.05） than controls.ITDs exceeding 60 bp in length were associated with decreasing OS as compared with shorter ITD in AML patients with FLT3-ITD mutation（ P〈0.05）.OS and RFS were similar among the 2 groups receiving consolidation chemotherapy.Besides,the patients with allo-HSCT had shorter ITDs and longer OS than ITDs exceeding 60 bp（ P〈0.05） and similar to AML patients without FLT3-ITD mutation.Conclusion： AML patients with FLT3-ITD mutation has poorer outcome,among which the prognosis was w orse in patients with ITD exceeding 60 bp,and the chemotherapy alone can not improve the prognosis of FLT3-ITD-＋.Allo-HSCT is an effective treatment for AML patients with FLT3-ITD mutation; Sorafenib appears to be an effective maintenance therapy after allo-HSCT in FLT3-ITD AML.
作者
陈芳
江雪杰
阴常欣
钟清秀
蒋玲
余国攀
孙竞
孟凡义
CHEN Fang;JIANG Xue-Jie;YIN Chang-Xin;ZHONG Qing-Xiu;JIANG Ling;YU Guo-Pan;SUN Jing;MENG Fan-Yi(Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China;Department of Hematology, Kanghua Hospital, Dongguan 523080, Guangdong Province, China)
出处
《中国实验血液学杂志》
CAS
CSCD
北大核心
2018年第3期678-683,共6页
Journal of Experimental Hematology
