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考虑基线因素和早期缓解率以优化慢性期慢性髓性白血病的治疗。

Considering baseline factors and early response rates to optimize therapy for chronic myeloid leukemia in chronic phase.

作者信息

Akard Luke P, Bixby Dale

机构信息

a Indiana Blood and Marrow Transplantation, Franciscan St Francis Hospital and Health Centers , Indianapolis , IN , USA ;

b Division of Hematology and Oncology, Department of Internal Medicine , University of Michigan Comprehensive Cancer Center , Ann Arbor , MI , USA.

出版信息

Leuk Lymphoma. 2016 May;57(5):1002-14. doi: 10.3109/10428194.2015.1122779. Epub 2016 Jan 4.

Abstract

Multiple BCR-ABL tyrosine kinase inhibitors (TKIs) are available for the treatment of chronic myeloid leukemia in chronic phase (CML-CP), and several baseline and on-treatment predictive factors have been identified that can be used to help guide TKI selection for individual patients. In particular, early molecular response (EMR; BCR-ABL ≤10% on the International Scale at 3 months) has become an accepted benchmark for evaluating whether patients with CML-CP are responding optimally to frontline TKI therapy. Failure to achieve EMR is considered an inadequate initial response according to the National Comprehensive Cancer Network guidelines and a warning response according to the European LeukemiaNet recommendations. Here we review data supporting the importance of achieving EMR for improving patients' long-term outcomes and discuss key considerations for selecting a frontline TKI in light of these data. Because a higher proportion of patients achieve EMR with second-generation TKIs such as nilotinib and dasatinib than with imatinib, these TKIs may be preferable for many patients, particularly those with known negative prognostic factors at baseline. We also discuss other considerations for frontline TKI choice, including toxicities, cost-effectiveness, and the emerging goals of deep molecular response and treatment-free remission.

摘要

多种BCR-ABL酪氨酸激酶抑制剂(TKIs)可用于治疗慢性期慢性髓性白血病(CML-CP),并且已经确定了几个基线和治疗期间的预测因素,可用于帮助指导为个体患者选择TKI。特别是,早期分子反应(EMR;3个月时国际量表上BCR-ABL≤10%)已成为评估CML-CP患者对一线TKI治疗是否有最佳反应的公认基准。根据美国国立综合癌症网络指南,未达到EMR被认为是初始反应不足,而根据欧洲白血病网络的建议则为警示反应。在此,我们回顾支持实现EMR对改善患者长期预后重要性的数据,并根据这些数据讨论选择一线TKI的关键考虑因素。由于与伊马替尼相比,使用第二代TKI(如尼罗替尼和达沙替尼)的患者达到EMR的比例更高,因此这些TKI可能对许多患者更可取,尤其是那些基线时有已知不良预后因素的患者。我们还讨论了一线TKI选择的其他考虑因素,包括毒性、成本效益以及深度分子反应和无治疗缓解等新出现的目标。

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