达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的临床研究

Efficacy of Dasatinib in Treatment of Imatinib-Resistant BCR/ABL Positive Leukemia

本研究评价达沙替尼治疗原发或继发伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性。对27例原发或继发伊马替尼耐药的慢性髓系白血病(CML)或Ph阳性急性淋巴细胞白血病(Ph+ALL)患者,给予达沙替尼100-140 mg/d口服治疗,评估疗效、总体生存和耐受情况。结果表明:27例伊马替尼耐药的BCR/ABL阳性白血病中位达沙替尼治疗时间8(1-66)个月,中位随访时间54(3-75)个月。27例接受达沙替尼治疗的患者中,88.8%获得完全血液学反应(CHR),44.4%获得主要细胞遗传学反应(mCyR),37%获得完全遗传学反应(CCyR),18.5%获得主要分子学反应(MMR)。伊马替尼耐药的进展期(CML-AP、CML-BC、骨髓复发Ph+ALL)患者接受达沙替尼治疗获CCyR率低于疾病稳定期(CML-CP、骨髓缓解Ph+ALL)患者(P=0.0377),且3-4级不良反应发生率明显增高。达沙替尼治疗后获得CCyR的患者生存期(OS)较未达CCyR者明显延长(63个月vs 9个月,P=0.0126)。达沙替尼治疗后最常见的3-4级不良反应包括血液学反应如血小板减少(51.8%)、中性粒细胞减少(48.1%)、贫血(33.3%)和非血液学反应如胸腔积液(18.5%)、肺部感染(18.5%)、心包积液(11.1%)。3-4级不良反应主要发生在疾病进展期时改服达沙替尼者,均发生于服药12个月内。结论:达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病有效,且在疾病稳定期改服达沙替尼疗效和耐受性更好。

This study was aimed to evaluate the efficacy and safety of dasatinih 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 achived complete hematologic response （CHR） , 29.6% of them achived major cytogenetic response （mCyR）, 37% of all achived complete cytogenetic response （CCyR） and 18.5% cases achived 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 occured more frequently in progress of disease than that in stable disease. Overall survival of the patients who achived CCyR after dasatinib therapy was statistically longer than those who did not achive 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 thrombocyto-penia （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 occared 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.