Soverini Simona, De Benedittis Caterina, Mancini Manuela, Martinelli Giovanni
Department of Experimental, Diagnostic and Specialty Medicine, Hematology/Oncology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy
Department of Experimental, Diagnostic and Specialty Medicine, Hematology/Oncology "L. e A. Seràgnoli," University of Bologna, Bologna, Italy.
Oncologist. 2016 May;21(5):626-33. doi: 10.1634/theoncologist.2015-0337. Epub 2016 Mar 31.
: Optimal use of current therapeutic opportunities for chronic myeloid leukemia patients requires integration of clinical and laboratory monitoring. Assessment of molecular response (MR) by real-time quantitative polymerase chain reaction is the most sensitive way to monitor tyrosine kinase inhibitor (TKI) treatment efficacy. Besides major molecular response, which has emerged as a safe haven for survival since the initial studies of first-line imatinib treatment, two additional MR milestones have recently been defined: early molecular response and deep molecular response. The achievement of such MR milestones within defined time points during therapy is thought to draw the ideal trajectory toward optimal long-term outcome and, possibly, successful treatment discontinuation. Sensitive and reproducible MR measurement and proper interpretation of MR results are therefore critical to correctly inform therapeutic decisions. In patients who do not achieve an optimal response to TKI therapy, BCR-ABL1 mutation screening should also be performed, because it may deliver useful information for TKI choice. This review aims to help clinicians apply and translate the latest response definitions and clinical recommendations into practice. We provide a critical update on how these recommendations have incorporated MR levels in the clinical decision algorithms and how detection of BCR-ABL1 mutations should be interpreted. We also include a practical guide for pathologists and molecular biologists to best perform molecular testing and for hematologists and oncologists to best integrate it into routine practice.
Ever-more-potent therapeutic strategies have been developed for chronic myeloid leukemia (CML) in parallel with the evolution of therapeutic goals and the refinement of response definitions and monitoring schemes and procedures. Terminology and methodology continue to evolve rapidly, making it difficult for busy hematology/oncology professionals to keep abreast of the newest developments. Optimal CML patient management results from the timely and rational use of molecular testing, the critical assessment of the power and pitfalls of current technology, and the appropriate interpretation and contextualization of results.
慢性髓性白血病患者要想最佳地利用当前的治疗机会，需要将临床监测与实验室监测相结合。通过实时定量聚合酶链反应评估分子反应（MR）是监测酪氨酸激酶抑制剂（TKI）治疗效果最敏感的方法。除了主要分子反应（自一线伊马替尼治疗的初始研究以来已成为生存的安全港）之外，最近还定义了另外两个MR里程碑：早期分子反应和深度分子反应。在治疗期间的特定时间点内实现这些MR里程碑被认为是朝着最佳长期结果以及可能成功停药绘制理想轨迹。因此，灵敏且可重复的MR测量以及对MR结果的正确解读对于正确指导治疗决策至关重要。对于未达到TKI治疗最佳反应的患者，也应进行BCR-ABL1突变筛查，因为这可能为TKI选择提供有用信息。本综述旨在帮助临床医生将最新的反应定义和临床建议应用并转化为实践。我们对这些建议如何将MR水平纳入临床决策算法以及应如何解读BCR-ABL1突变检测进行了重要更新。我们还为病理学家和分子生物学家提供了一份实用指南，以最佳地进行分子检测，为血液学家和肿瘤学家提供了一份实用指南，以最佳地将其整合到常规实践中。
随着治疗目标的演变以及反应定义和监测方案及程序的完善，针对慢性髓性白血病（CML）开发了越来越有效的治疗策略。术语和方法仍在迅速发展，这使得忙碌的血液学/肿瘤学专业人员难以跟上最新进展。最佳的CML患者管理源于分子检测的及时合理使用、对当前技术的优势和缺陷的批判性评估以及对结果的适当解读和背景化。
