Objective: To evaluate the efficacy and prognostic factors in core binding factor (CBF) acute myeloid leukemia (AML) under current therapy modalities, therefore optimizing the treatment strategies. Methods: Standard cytological and immune methods including next generation sequencing (NGS) were used for risk stratification. Complete remission (CR) rate, disease-free survival (DFS) and overall survival (OS) were assessed by multivariate Logistic and Cox regression models in a total of 206 adults (aged 16-65 years) with CBF-AML, including 152 AML patients with t(8;21) and 54 with inv(16). Results: The CR rate of inv(16) patients after first course was 54/54(100%), significantly higher than that of t(8;21) patients [127/147(86.4%), P=0.005]. The fusion transcript level and KIT mutation were independent factors related to CR rate in t(8;21) patients (P=0.044 and 0.027; respectively). DFS and OS in inv(16) patients tended to be more superior than that in t(8;21) patients (P=0.066 for DFS; P=0.306 for OS; respectively). Multivariate Cox identified negative expression of CD(19) and female gender the independent predictors of inferior DFS in t(8;21) patients (P=0.000 for CD(19); P=0.006 for sex; respectively). Analysis of combining CD(19) with gender indicated that females/CD(1)(9-)subpopulation had significantly poor DFS than did males/CD(19)(+) ones (Bonferroni-P<0.000 01). The number of mutations in each patient, FLT3-ITD and additional karyotype abnormalities did not affect CR rate and DFS (all P>0.05). Conclusions: Patients with inv(16) have better induction response than those with t(8;21). High level of fusion transcripts and positive KIT mutation are associated with low CR rate in t(8;21) patients. Negative CD(19) expression and female gender are independent predictors of inferior DFS in t(8;21) patients.
目的： 综合运用传统细胞形态学、免疫学、细胞遗传学和分子生物学（MICM）分型结合二代测序，评价当前诱导和巩固模式下，核心结合因子相关急性髓系白血病（CBF-AML）的疗效和预后因素，以进一步优化CBF-AML的治疗选择。 方法： 收集206例成人初治CBF-AML患者，年龄16~65岁，包括152例t(8;21)AML和54例inv(16)AML。采用多因素logistic和Cox回归模型，分析MICM分型结合51种二代测序基因突变特征对完全缓解（CR）率、无病生存（DFS）和总生存（OS）的影响。 结果： 标准方案诱导1个疗程后，inv(16)AML患者的CR率为100%(54/54)，显著高于t(8;21)AML患者的86.4%(127/147)(P=0.005)。融合转录本水平和KIT突变是t(8;21)AML患者CR率的独立影响因素（P值分别为0.044和0.027)。inv(16)AML患者的DFS和OS有优于t(8;21)AML患者的趋势，但尚无统计学意义（P值分别为0.066和0.306)。多因素Cox分析显示，CD(1)(9－)和女性是t(8;21)AML患者不良DFS的独立预测因素（CD(19)：P=0.000；性别：P=0.006)。CD(19)和性别结合的分析显示，女性CD(1)9－患者的DFS显著差于男性CD(19)(+)患者（Bonferroni检验，P<0.000 01)。每例患者基因突变个数、FLT3-ITD和附加核型异常不影响CR率和DFS(P值均>0.05)。 结论： inv(16)AML患者的诱导疗效优于t(8;21)AML患者。t(8;21)AML患者高融合转录本水平或阳性KIT突变与低CR率有关，且CD(19)阴性表达、女性因素可预测复发增加。.
Keywords: Antigens, CD(19); Core binding factors; Leukemia, myeloid, acute; Prognosis; t(8;21).