FLT3-ITD与DNMT3A R882双突变对异基因造血干细胞移植后急性髓系白血病预后的影响

[Effect of FLT3-ITD with DNMT3A R882 double-mutation on the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation].

作者信息

Tang S H, Lu Y, Zhang P S, Liu X H, Du X H, Chen D, Sha K Y, Li S Y, Cao J J, Chen L G, Zhuang X X, Pei R Z, Tang X W

机构信息

Department of Hematology, Yinzhou People Hospital, Ningbo 315040, China.

出版信息

Zhonghua Xue Ye Xue Za Zhi. 2018 Jul 14;39(7):552-557. doi: 10.3760/cma.j.issn.0253-2727.2018.07.005.

DOI:10.3760/cma.j.issn.0253-2727.2018.07.005

PMID:30122013

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7342207/

Abstract

To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, <0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, <0.05]. AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.

摘要

探讨FLT3-ITD和DNMT3A R882双突变对异基因造血干细胞移植（allo-HSCT）后急性髓系白血病预后的影响。采用Sanger测序法检测206例新诊断急性髓系白血病患者的FLT3-ITD、DNMT3A、C-kit、CEBPA、FLT3-TKD和NPM1突变（排除M3型及接受FLT3抑制剂治疗的患者）。回顾性分析急性髓系白血病患者的临床资料，比较各基因突变组的预后。①206例患者中，男性104例，女性102例，中位年龄38（3-63）岁，其中M0型6例，M1型24例，M2型56例，M4型39例，M5型63例，M6型6例，未分类12例。②206例患者根据诊断时的突变基因分为四组：FLT3-ITD(+)DNMT3A R882(+)组（A组）、FLT3-ITD(+)DNMT3A R882(-)组（B组）、FLT3-ITD(-)DNMT3A R882(+)组（C组）和FLT3-ITD(-)DNMT3A R882(-)组（D组）。四组患者的性别、诊断时白细胞计数、染色体核型、中位年龄、FAB分型、移植前疾病状态、供者类型、预处理方案及移植物抗宿主病差异均无统计学意义（>0.05）。③A组2年累积复发率（CIR）显著高于其他组[A组（72.2±2.6）%，B组（38.6±0.6）%，C组（36.8±1.6）%，D组（27.8±0.1）%，P<0.05]，而2年总生存（OS）率和2年无白血病生存（LFS）率低于其他组[A组（30.9±13.3）%，（11.3±10.2）%；B组（67.5±7.8）%，（47.9±8.4）%；C组（61.4±12.4）%，（56.8±12.5）%；D组（80.1±3.7）%，（79.7±3.6）%，P<0.05]。FLT3-ITD和DNMT3A R882双突变的急性髓系白血病患者移植后CIR很高，OS、LFS很低。