Faculty of Medicine, University of Southampton, Southampton, UK.
Leukemia. 2012 Oct;26(10):2172-5. doi: 10.1038/leu.2012.104. Epub 2012 Apr 16.
The International Randomized Study of Interferon and STI571 (IRIS) demonstrated long-term cytogenetic responses in patients with chronic-phase chronic myeloid leukemia (CML-CP) treated with the tyrosine kinase inhibitor (TKI) imatinib. However, deep molecular responses (MRs), as measured by reductions in BCR-ABL transcript levels below the threshold of major MR, were achieved only by a small proportion of patients. With the advent of the second-generation TKIs nilotinib and dasatinib for the treatment of patients with newly diagnosed CML-CP, the proportion of patients who achieve the deepest levels of MR is likely to increase significantly. With these changes, the potential for patient eligibility in TKI cessations studies is becoming a more widely discussed topic and area for research. These developments highlight the need for robust, standardized and workable definitions of deep MRs. Specifically, it is critical that the measurement of MR is standardized in a manner to withstand both intra- and inter-laboratory variability, as well as new methodological developments. This review summarizes the relevant clinical background and proposes a framework within which standardization of MR can be taken forward.
国际随机干扰素和 STI571 研究（IRIS）表明，接受酪氨酸激酶抑制剂（TKI）伊马替尼治疗的慢性期慢性髓性白血病（CML-CP）患者可获得长期细胞遗传学反应。然而，只有一小部分患者通过降低 BCR-ABL 转录水平达到主要分子反应（MR）以下的阈值来实现深度分子反应（MR）。随着第二代 TKI 尼洛替尼和达沙替尼用于治疗新诊断的 CML-CP 患者，达到最深水平 MR 的患者比例可能会显著增加。随着这些变化，TKI 停药研究中患者资格的潜力成为一个更广泛讨论的话题和研究领域。这些发展突显了稳健、标准化和可行的深度 MR 定义的必要性。具体来说，至关重要的是，以能够承受实验室内部和实验室之间变异性以及新方法学发展的方式标准化 MR 的测量。本综述总结了相关的临床背景，并提出了一个可以推进 MR 标准化的框架。
