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中华临床医师杂志(电子版) ›› 2019, Vol. 13 ›› Issue (08) : 589 -595. doi: 10.3877/cma.j.issn.1674-0785.2019.08.006

所属专题: 文献

临床研究

联合CD19和KITD816进一步优化t(8;21)急性髓系白血病预后分层
王彪1, 林榕榕1, 杨斌1, 李海乾1, 邢姗姗2, 张修文3, 谢晓宝1, 严峰1,()   
  1. 1. 213000 江苏常州,常州市第一人民医院血液科
    2. 310013 浙江杭州,浙江医院血液科
    3. 213000,江苏常州,南京医科大学附属常州二院血液科
  • 收稿日期:2019-02-16 出版日期:2019-04-15
  • 通信作者: 严峰

CD19 combined with KITD816 for optimization of prognostic stratification of t(8; 21) acute myeloid leukemia

Biao Wang1, Rongrong Lin1, Bin Yang1, Haiqian Li1, Shanshan Xing2, Xiuwen Zhang3, Xiaobao Xie1, Feng Yan1,()   

  1. 1. Department of Hematology, Changzhou First People's Hospital, Changzhou 213000, China
    2. Department of Hematology, Zhejiang Hospital, Hangzhou 310013, China
    3. Department of Hematology, Nanjing Medical University Affiliated Changzhou Second Hospital, Changzhou 213000, China
  • Received:2019-02-16 Published:2019-04-15
  • Corresponding author: Feng Yan
  • About author:
    Corresponding author: Yan Feng, Email:
引用本文:

王彪, 林榕榕, 杨斌, 李海乾, 邢姗姗, 张修文, 谢晓宝, 严峰. 联合CD19和KITD816进一步优化t(8;21)急性髓系白血病预后分层[J/OL]. 中华临床医师杂志(电子版), 2019, 13(08): 589-595.

Biao Wang, Rongrong Lin, Bin Yang, Haiqian Li, Shanshan Xing, Xiuwen Zhang, Xiaobao Xie, Feng Yan. CD19 combined with KITD816 for optimization of prognostic stratification of t(8; 21) acute myeloid leukemia[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2019, 13(08): 589-595.

目的

分析当前治疗模式下的t(8;21)急性髓系白血病(AML)患者的缓解和预后异质性,为进一步个体化治疗提供依据。

方法

收集2014年10月至2018年9月常州市第一人民医院107例标准方案诱导的成人初治t(8;21)AML患者,综合传统MICM和二代测序(NGS)基因突变特征,应用多因素Logistic和Cox回归分析,评价完全缓解(CR)率、累积复发率、无事件生存(EFS)和总生存(OS)的影响因素。

结果

诱导1个疗程后,CR率为79.0%(83/105),早期死亡率为1.9%(2/107)。多因素分析显示,KIT-D816突变阳性是不良影响CR率[HR=3.29(1.18~9.24),P=0.023]、EFS[HR=3.53(1.82~6.84),P=0.000]和OS[HR=5.45(1.77~16.84),P=0.003]的唯一独立因素。CD19表达阴性是唯一独立预测累积复发率增加的不利因素[HR=0.32(0.10~1.00),P=0.050]。而KIT突变、KIT-N822和复杂核型对任何终点均不构成独立意义。

结论

建议将特定的KIT-D816突变而非KIT突变纳入t(8;21)AML危险分层体系;CD19表达阴性的t(8;21)AML患者复发风险增加,需密切监测。

Objective

To analyze the heterogeneity of remission and prognosis of patients with t(8; 21) acute myeloid leukemia (AML) under current treatment modalities, and to provide a basis for further risk-adapted treatment.

Methods

A total of 107 adult patients with primary t(8; 21) AML treated with the standard 3+ 7 regimen at Changzhou First People's Hospital from October 2014 to September 2018 were collected. The complete remission (CR) rate, cumulative incidence of relapse, event-free survival (EFS), and overall survival (OS) were evaluated by combining the characteristics of traditional Morphology, Immunology, Cytogenetics, and Molecular biology (MICM) and genetic mutations based on next-generation sequencing (NGS) using multivariate Logistic and Cox regression analyses.

Results

After a single induction course, the CR rate was 79.0% (83/105) and the early mortality rate was 1.9% (2/107). Multivariate analysis showed that positive KIT-D816mut was the only independent factor adversely affecting the CR rate (hazard ratio [HR]=3.29 [1.18-9.24], P=0.023), EFS (HR=3.53 [1.82-6.84], P=0.000), and OS (HR=5.45 [1.77-16.84], P=0.003). Negative CD19 expression was the only independent predictor of increased cumulative incidence of relapse (HR=0.32 [0.10-1.00], P=0.050). KITmut, KIT-N822, and complex karyotype were not independent risk factors for all endpoints.

Conclusions

It is suggested that the specific KIT-D816mut, rather than general KITmut, should be included in the risk stratification system of t(8; 21) AML. Patients with negative CD19 have an increased risk of relapse, which requires close monitoring.

表1 107例初诊t(8;21)患者基本资料、MICM分型和基因突变特征
因素 数值
年龄[岁,中位数(范围)] 36(16~67)
? 年龄<35[例(%)] 50(46.7)
? 年龄≥35[例(%)] 57(53.3)
性别(男/女) 57/50
WBC计数[×109/L,中位数(范围)] 8.7(1.3~155.0)
? WBC<10[例(%)] 58(54.2)
? WBC≥10[例(%)] 49(45.8)
Hb水平[g/L,中位数(范围)] 74(39~145)
? Hb<80[例(%)] 68(63.6)
? Hb≥80[例(%)] 39(36.4)
PLT计数[×109/L,中位数(范围)] 28(2~195)
? PLT<30[例(%)] 57(53.3)
? PLT≥30[例(%)] 50(46.7)
RUNX1-RUNX1T1定量[copies/ABL copies,中位数(范围)] 179.4(28.1~675.0)
? Fusion transcript<150[例(%)] 28/70(40.0)
? Fusion transcript≥150[例(%)] 42/70(60.0)
WT1定量[copies/ABL copies,中位数(范围)] 22.7(0.2~312.7)
? WT1<30[例(%)] 31/57(54.4)
? WT1≥30[例(%)] 26/57(45.6)
免疫表型[n/N(%)]a ?
? CD34 105/105(100)
? TdT 24/101(23.8)
? HLA-DR 104/105(99.0)
? CD117 105/105(100.0)
? CD13 101/105(96.2)
? CD33 103/105(98.1)
? CD123 100/101(99.0)
? CD38 101/103(98.1)
? CD64 6/90(6.7)
? CD56 81/96(84.4)
? MPO 100/101(99.0)
? CD9 30/68(44.1)
? CD19 79/105(75.2)
? CD79a 22/101(21.8)
? CD7 13/96(13.5)
细胞遗传学[例(%)] ?
? 单独t(8;21) 39(36.4)
? 附加LOS 52(48.6)
? 附加del(9q) 3(2.8)
? 附加≥2个其他异常 12(11.2)
? 附加≥3个其他异常 8(7.5)
? 变异性复杂易位 7(6.5)
基因突变[n/N(%)]a ?
? 信号传导通路 ?
? ? KIT 47/95(49.5)
? ? KIT-D816 29/95(30.5)
? ? KIT-N822 17/95(17.9)
? ? NRAS 14/95(14.7)
? ? FLT3 12/95(12.6)
? ? FLT3-ITD 7/95(7.4)
? ? FLT3其他 5/95(5.3)
? ? CSF3R 8/95(8.4)
? ? RELN 8/95(8.4)
? ? JAK2 8/95(8.4)
? ? NOTCH1 10/95(10.5)
? ? SH2B3 8/95(8.4)
? 表观遗传学调节 ?
? ? KMT2D 10/95(10.5)
? ? TET2 8/95(8.4)
? ? ASXL1 9/95(9.5)
? ? EP300 6/95(6.3)
? ? CREBBP 6/95(6.3)
? 肿瘤抑制因子(FAT1) 14/95(14.7)
突变个数[中位数(范围)] 3(0~11)
表2 t(8;21)患者CR率多因素Logistic回归分析
表3 t(8;21)患者累积复发率多因素Cox分析
图1,2 累积复发率生存曲线 图1为CD19阳性和阴性患者的累积复发率;图2为KIT-D816阳性和阴性患者的累积复发率
表4 t(8;21)患者EFS多因素Cox分析
图3,4 无事件生存率生存曲线 图3为CD19表达阳性和阴性患者的无事件生存率,图4为KIT-D816突变阳性或阴性的患者的无事件生存率
表5 t(8;21)患者OS多因素Cox分析
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