达沙替尼联合化疗治疗7例儿童核心结合因子阳性急性髓系白血病患儿疗效评估

The curative effect of dasatinib treatment on 7 children with core binding factor positive acute myeloid leukemia

目的:对达沙替尼作为第二代酪氨酸激酶抑制剂靶向抑制存在C-KIT突变及KIT蛋白高表达的核心结合因子阳性的急性髓系白血病(AML)患儿的临床有效性和安全性进行评估。方法:选取我中心7例核心结合因子阳性的AML患儿,完善其发病时白细胞总数、骨髓形态、流式免疫分型、染色体核型分析、融合基因定量及突变基因筛查,给予达沙替尼单药治疗或者联合化疗治疗,根据血药物浓度,调整达沙替尼用量,以15天为1个周期评估患儿骨髓形态、流式免疫分型、融合基因定量拷贝数的变化情况。结果:4例患儿经达沙替尼治疗后融合基因降低至低拷贝数,其中2例C-KIT突变的患儿接受治疗后融合基因均降至低拷贝数。1例巩固治疗5个疗程后融合基因高拷贝数的患儿单用达沙替尼,15天融合基因降至低拷贝数。结论:达沙替尼可以增加化疗对核心结合因子阳性的AML的疗效,尤其是存在C-KIT突变及KIT蛋白过表达的患儿。

Objective：To investigate the effect and safety of dasatinib which as the second generation of TKIs can be targeted to inhibit downstream pathways of C-KIT mutation and KIT protein over-expression in core binding factor positive acute myeloid leukemia（AML）.Method：Seven cases of core binding factor positive AML were collected in our center.The data of total white blood cell counts,bone marrow morphology,flow cytometry immunophenotype,karyotype analysis,quantitative analysis of fusion gene and gene mutation were acquired.Dasatinib was admitted as mono-therapy or combined with chemotherapy.According to the blood drug concentration,its dosage was adjusted.We assessed the bone marrow morphology,flow cytometry immunophenotype,quantitative analysis of fusion gene for every 15 days.Result：The quantity of fusion gene in 4patients decreased to the lower level.Two C-KIT positive children obtained good response.A child with high level of fusion gene copies after 5courses consolidation therapy obtained lower level in 15 days treatment of dasatinib mono-therapy.Conclusion：Dasatinib can increase chemotherapy curative effect of core binding factor positive AML,especially for the children with CKIT mutation and over-expression of KIT protein.