Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA.
Cancer. 2010 Mar 15;116(6):1419-30. doi: 10.1002/cncr.24928.
Identification of BCR-ABL as the defining leukemogenic event in chronic myelogenous leukemia (CML) revolutionized the treatment of the disease. Imatinib, a potent BCR-ABL inhibitor, is the standard of care for the first-line treatment of patients with chronic-phase CML because of its high long-term response rates and favorable tolerability profile compared with previous standard therapies. However, resistance to imatinib develops in 2% to 4% of patients annually. For patients with acquired cytogenetic resistance to standard-dose imatinib (400 mg daily), imatinib dose escalation (600-800 mg daily) is an excellent first option for managing patients and achieving cytogenetic responses. However, for patients with primary resistance to imatinib, hematologic disease recurrence, or emergent BCR-ABL kinase domain mutations, imatinib dose escalation may not be sufficient to control the disease. For these patients, the potent second-generation tyrosine kinase inhibitors dasatinib and nilotinib are available. Both agents provide effective therapeutic options for patients with imatinib resistance or intolerance. For the current overview, the authors reviewed the data supporting the use of both dasatinib and nilotinib in imatinib-resistant or imatinib-intolerant patients, and they have highlighted the future of CML therapy. Overall, the article is intended to offer physicians a comprehensive review of the current literature and to provide data supporting various treatment options for patients with CML throughout the course of imatinib therapy and beyond.
BCR-ABL 的鉴定作为慢性髓性白血病（CML）的致病事件，彻底改变了这种疾病的治疗方法。伊马替尼是一种强效的 BCR-ABL 抑制剂，由于其与先前的标准疗法相比具有更高的长期缓解率和良好的耐受性，因此成为慢性期 CML 患者一线治疗的标准治疗方法。然而，每年仍有 2%至 4%的患者会产生对伊马替尼的耐药性。对于获得对标准剂量伊马替尼（400mg 每日）的细胞遗传学耐药的患者，伊马替尼剂量升级（每日 600-800mg）是管理患者和实现细胞遗传学反应的绝佳首选。然而，对于对伊马替尼原发性耐药、血液学疾病复发或出现 BCR-ABL 激酶结构域突变的患者，伊马替尼剂量升级可能不足以控制疾病。对于这些患者，可使用强效的第二代酪氨酸激酶抑制剂达沙替尼和尼洛替尼。这两种药物都为对伊马替尼耐药或不耐受的患者提供了有效的治疗选择。在本次综述中，作者回顾了支持达沙替尼和尼洛替尼在伊马替尼耐药或不耐受患者中应用的数据，并强调了 CML 治疗的未来。总的来说，本文旨在为医生提供对当前文献的全面回顾，并提供数据支持伊马替尼治疗过程中和之后 CML 患者的各种治疗选择。
