二代酪氨酸激酶抑制剂达沙替尼治疗慢性髓性白血病安全性研究进展

Advance of safety study of the second generation tyrosine kinase inhibitor dasatinib in patients with chronic myeloid leukemia

慢性髓性白血病（CML）是一种起源于造血干细胞的恶性增殖性疾病。目前经酪氨酸激酶抑制剂（TKI）治疗的CML患者生存期接近一般人群,在其治疗过程中依从性和持续性尤为重要,在TKI中进行药物选择时,安全谱是必须考量的因素。二代TKI达沙替尼对导致伊马替尼耐药的100多种BCR-ABL突变有效[1],

Summary Chronic myeloid leukemia （CML） is a malignant hematopoietic myeloproliferative neoplasm char- acterized in 95 % of cases by t（9：22） （q34;q11）, the fusion of Abelson leukemia virus （ABL） gene on chromosome 9 with the breakpoint cluster region （BCR） gene on chromosome 22, resulting in BCR-ABL fusion gene （Philadel- phia chromosome,Ph） and protein,which account for the molecular patbogenesis of CML occurrence and develop- ment. As the first generation of tyrosine kinase inhibitor （TKI） targeting BCR-ABL activity,imatinib mesylate has revolutionized the treatment of CML and transformed CML into a manageable ~chronic~ disorder,but resistance as well as intolerance has emerged as a significant clinical concern. Dasatinib is one of the second-generation TKIs that can achieve faster and deeper molecular responses with a favorable safety profile, and its related hematologic and non-hematologic adverse events （AE） are predominantly mild to moderate, self-limiting, reversible or managea- ble. While choosing a TKI treatment, balancing expected benefits with tolerance and resistance should be taken into consideration. Early detection and proper intervention of AE can minimize the potential risk and damage, increase patients adherence and persistence, as well as quality of life, which is important for patients with lifelong CML treatment.