[FLT3-ITD突变及ITD长度对急性髓系白血病患者预后的影响]
[Influence of FLT3-ITD Mutation and ITD Length on the Outcome on Patients with Acute Myeloid Leukemia].
作者信息
Chen Fang, Jiang Xue-Jie, Yin Chang-Xin, Zhong Qing-Xiu, Jiang Ling, Yu Guo-Pan, Sun Jing, Meng Fan-Yi
机构信息
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
Department of Hematology, Kanghua Hospital, Dongguan 523080, Guangdong Province, China.
出版信息
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2018 Jun;26(3):678-683. doi: 10.7534/j.issn.1009-2137.2018.03.008.
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 BM blast 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 worse 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.
目的
探讨FLT3-ITD突变及ITD长度对非M3型急性髓系白血病患者总生存期（OS）及无复发生存期（RFS）的影响。
方法
回顾性分析2011年6月至2016年4月期间75例FLT3-ITD突变的急性髓系白血病（AML）患者及76例核型正常的FLT3-ITD AML患者的临床特征及治疗效果。采用聚合酶链反应（PCR）扩增基因组DNA，对40例患者进行DNA测序分析FLT3-ITD突变长度。
结果
FLT3-ITD突变的AML患者初诊时白细胞计数更高，骨髓原始细胞比例也高于无FLT3-ITD突变的AML患者（95.13对10.85）（P<0.01）；72%对59%（P<0.01）。FLT3-ITD突变的AML患者完全缓解（CR）率低于无FLT3-ITD突变的AML患者（70.42%对94.7%）（P<0.01）。与接受巩固化疗的患者相比，接受异基因造血干细胞移植（allo-HSCT）的AML患者OS（P<0.01）和RFS（P<0.01）显著延长，且与无FLT3-ITD突变接受HSCT的AML患者相似。HSCT后接受索拉非尼维持治疗的患者OS（P<0.05）和RFS（P<0.05）均长于对照组。与FLT3-ITD突变的AML患者中较短ITD相比，长度超过60 bp的ITD与OS降低相关（P<0.05）。两组接受巩固化疗的患者OS和RFS相似。此外，接受allo-HSCT的患者ITD较短，OS长于长度超过60 bp的患者（P<0.05），且与无FLT3-ITD突变的AML患者相似。
结论
FLT3-ITD突变的AML患者预后较差，其中ITD超过60 bp的患者预后更差，单纯化疗不能改善FLT3-ITD的预后。allo-HSCT是治疗FLT3-ITD突变AML患者的有效方法；索拉非尼似乎是FLT3-ITD AML患者allo-HSCT后有效的维持治疗药物。
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