Clinical effect of dasatinib in treatment of imatinib-resistant chronic myeloid leukemia blast crisis
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摘要: 目的:评价达沙替尼治疗伊马替尼耐药的BCR-ABL阳性慢性髓细胞白血病急变期(CML-BC)的疗效和安全性。方法:对7例伊马替尼耐药的CML-BC患者,给予达沙替尼100 mg/d口服治疗,观察达沙替尼对CML患者的血液学、遗传学及分子生物学反应,并监测不良反应,评估疗效和耐受情况。结果:7例伊马替尼耐药的BCR-ABL阳性CML-BC患者服用达沙替尼治疗后均获得完全血液学缓解,4例达到完全细胞遗传学缓解,1例达到完全分子学反应。4例达沙替尼治疗后检测到突变,4例死亡。2例出现3~4级中性粒细胞减少和3~4级血小板减少。结论:达沙替尼治疗伊马替尼耐药的BCR-ABL阳性CML-BC患者起效迅速,可获得完全血液学及细胞遗传学缓解,甚至获得完全分子生物学缓解,但维持时间短,容易再次出现疾病进展。达沙替尼治疗后可出现新的ABL激酶区突变,导致患者对达沙替尼耐药。
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关键词:
- 达沙替尼 /
- 白血病,髓细胞,慢性 /
- 耐药 /
- 突变
Abstract: Objective:To evaluate the efficacy and safety of dasatinib in blastic-phase chronic myeloid leukemia (CML) with resistance to imatinib.Method:Seven patients with imatinib-resistant CML received dasatinib 100 mg/d orally.We observed the hematologic,cytogenetic remission and molecular response and recorded the occurrence of side effects.The overall survival and tolerance were evaluated and monitored.Result:After the dasatinib treatment,all patients achieved complete hematologic response (CHR),4 cases achieved complete cytogenetic response (CCyR),1 case achieved complete molecular response (CMR).Mutation had been detected in 4 cases after dasatinib treatment,and 4 cases died.Three to four grade neutropenia and thrombocytopenia occurred on 2 patients.Conclusion:Dasatinib is an effective drug in imatinib-resistant BCR-ABL positive blastic-phase CML,and some patients could achieve CHR and CCyR,even CMR.But it could not maintain a long time,and disease progression will happen again.New mutations in ABL kinase domain are occurred in dasatinib treated patients wich leading to dasatinib-resistant.-
Key words:
- dasatinib /
- chronic myeloid leukemia /
- resistant /
- mutation
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[1] Pui CH,Evans WE.Treatment of acute lymphoblastic leukemia[J].N Engl J Med,2006,354:166-178.
[2] Marin D,Bazeos A,Mahon FX,et al.Adherence is the critical factor for achieving molecular responses in patients with chronic myeloid leukemia who achieving complete cytogenetic responses on imatinib[J].J Clin Oncol,2010,28:2381-2388.
[3] McCormack PL,Keam SJ.Dasatinib:a review of its use in the treatment of chronic myeloid leukaemia and Philadelphia chromosome positive acute lymphoblastic leukaemia[J].Drugs,2011,71:1771-1795.
[4] Porkka K,Koskenvesa P,Lundan T,et al.Dsatinib crosses the lood-brain barrier and is an efficient therapy for central nervous system Philadelpphia chromosome-positive leukemia[J].Blood,2008,112:1005-1012.
[5] Johansson B,Fioretos T,Mitelman F.Cytogenetic and molecular genetic evolution of chronic myeloid leukemia[J].Acta Haematol,2002,107:76-94.
[6] Muvarak N,Nagaria P,Rassool FV.Genomic instability in chronic myeloid leukemia:targets for therapy[J].Curr Hematol Malig Rep,2012,7:94-102.
[7] Skorski T.Genetic mechanisms of chronic myeloid leukemia blastic transformation[J].Curr Hematol Malig Rep,2012,7:87-93.
[8] Soverini S,De Benedittis C,Papayannidis C,et al.Drug resistance and BCR-ABL kinase domain mutations in philadelphia chromosome-positive acute lymphoblastic leukemia from the imatinib to the second-generation tyrosine kinase inhibitor era[J].Cancer,2014,120:1002-1009.
[9] Razga F,Jurcek T,Zackova D,et al.Role of treatment in the appearance and selection of BCR-ABL1 kinase domain mutations[J].Mol Diagn Ther,2014,16:251-259.
[10] McCormack PL,Keam SJ.Spotlight on dasatinib in chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia[J].Bio Drugs,2012,26:61-64.
[11] Latif AL,McQuaker G,Parker A,et al.Allogeneic stem cell transplantation for chronic myeloid leukaemia is safe and effective in high risk patients following second generation tyrosine kinase inhibitors:a single centre's experience[J].Leuk Res Rep,2013,2:47-50.
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