Zhu Yu, Pan Liang-Qin, Qian Si-Xuan, Song Ping, Yu Hui, Zhang Su-Jiang, Ge Zheng, Hong Ming, Tian Tian, Li Jian-Yong
Department of Hematology, Jiangsu Province People's Hospital, Nanjing, Jiangsu Province, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2013 Jun;21(3):581-6. doi: 10.7534/j.issn.1009-2137.2013.03.009.
This study was aimed to evaluate the efficacy and safety of dasatinib in BCR/ABL positive leukemia patients with primary or secondary resistance to imatinib. 27 patients with primary or secondary imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia chromosome positive acute lymphocytic leukemia (Ph(+) ALL) received 100 - 140 mg/d dasatinib orally. Their overall survival and tolerance were evaluated. The results showed that the median duration of dasatinib therapy was 8 (1-66) months in the 27 imatinib-resistant BCR/ABL positive leukemia cases, with a median follow-up of 54 (3-75) months. After the dasatinib treatment, 88.8% of all the 27 cases achieved complete hematologic response (CHR), 29.6% of them achieved major cytogenetic response (mCyR), 37% of all achieved complete cytogenetic response (CCyR) and 18.5% cases achieved major molecular response (MMR). Patients who received dasatinib in progress of disease (CML-AP, CML-BC and bone marrow relapse Ph(+) ALL) had a lower CCyR rate than those in stable disease (CML-CP and bone marrow remission Ph(+) ALL) (P = 0.0377), and 3 - 4 grade adverse events occurred more frequently in progress of disease than that in stable disease. Overall survival of the patients who achieved CCyR after dasatinib therapy was statistically longer than those who did not achieve CCyR (63 m vs 9 m, P = 0.0126). The most common grade 3 - 4 adverse events during dasatinib therapy including hematology events such as thrombocytopenia (51.8%), neutropenia (48.1%), anemia (33.3%), and non-hematologic events such as pleural effusion (18.5%), pulmonary infection (18.5%), pericardial effusion (11.1%). The 3-4 grade adverse events occurred within 12 months from dasatinib therapy, and were mainly observed in patients with progress of disease. It is concluded that dasatinib is an effective drug in imatinib-resistant BCR/ABL positive leukemia patients, the better curative effect and better tolerance has been observed in patients who received dasatinib in stable disease.
本研究旨在评估达沙替尼对伊马替尼原发性或继发性耐药的BCR/ABL阳性白血病患者的疗效和安全性。27例原发性或继发性伊马替尼耐药的慢性粒细胞白血病（CML）或费城染色体阳性急性淋巴细胞白血病（Ph(+) ALL）患者口服100 - 140 mg/d达沙替尼。评估其总生存期和耐受性。结果显示，在27例伊马替尼耐药的BCR/ABL阳性白血病病例中，达沙替尼治疗的中位持续时间为8（1 - 66）个月，中位随访时间为54（3 - 75）个月。达沙替尼治疗后，27例患者中88.8%达到完全血液学缓解（CHR），29.6%达到主要细胞遗传学缓解（mCyR），37%达到完全细胞遗传学缓解（CCyR），18.5%达到主要分子学缓解（MMR）。疾病进展期（CML-AP、CML-BC和骨髓复发Ph(+) ALL）接受达沙替尼治疗的患者CCyR率低于疾病稳定期（CML-CP和骨髓缓解Ph(+) ALL）患者（P = 0.0377），3 - 4级不良事件在疾病进展期比稳定期更频繁发生。达沙替尼治疗后达到CCyR的患者总生存期在统计学上长于未达到CCyR的患者（63个月对9个月，P = 0.0126）。达沙替尼治疗期间最常见的3 - 4级不良事件包括血液学事件，如血小板减少（51.8%）、中性粒细胞减少（48.1%）、贫血（33.3%），以及非血液学事件，如胸腔积液（18.5%）、肺部感染（18.5%）、心包积液（11.1%）。3 - 4级不良事件在达沙替尼治疗后12个月内发生，主要见于疾病进展期患者。结论是，达沙替尼对伊马替尼耐药的BCR/ABL阳性白血病患者是一种有效的药物，在疾病稳定期接受达沙替尼治疗的患者观察到更好的疗效和耐受性。
