PDF(Pubmed)
Abstract：
The introduction of imatinib in 2000 opened the era of tyrosine kinase inhibitors (TKIs) for CML therapy and has revolutionized the life expectancy of CML patients, which is now quite like the one of the healthy aged population. Over the last 20 years, both the TKI therapy itself and the objectives have undergone evolutions highlighted and discussed in this review. The main objective of the CML therapy in the first 10 years after TKI introduction was to abolish the disease progression from the chronic to the blastic phase and guarantee the long-term survival of the great majority of patients. In the second 10 years (from 2010 to the present), the main objective of CML therapy moved from survival, considered achieved as a goal, to treatment-free remission (TFR). Two phenomena emerged: no more than 50-60% of CML patients could be candidates for discontinuation and over 50% of them molecularly relapse. The increased cumulative incidence of specific TKI off-target side effects was such relevant to compel to discontinue or reduce the TKI administration in a significant proportion of patients and to avoid a specific TKI in particular settings of patients. Therefore, the treatment strategy must be adapted to each category of patients. What about the patients who do not get or fail the TFR? Should they be compelled to continue the TKIs at the maximum tolerated dose? Alternative strategies based on the principle of minimal effective dose have been tested with success and they are now re-evaluated with more attention, since they guarantee survival and probably a better quality of life, too. Moving from treating the disease to treating the patient is an important change of paradigm. We can say that we are entering a personalized CML therapy, which considers the patients\' age, their comorbidities, tolerability, and specific objectives. In this scenario, the new techniques supporting the monitoring of the patients, such as the digital PCR, must be considered. In the present review, we present in deep this evolution and comment on the future perspectives of CML therapy.
摘要：
2000年伊马替尼的推出开启了酪氨酸激酶抑制剂（TKIs）用于CML治疗的时代，并彻底改变了CML患者的预期寿命。现在很像健康的老年人口。在过去的20年里,TKI治疗本身和目标都经历了演变,在本综述中强调和讨论.在TKI引入后的前10年中，CML治疗的主要目标是消除疾病从慢性期到发育期的进展，并确保绝大多数患者的长期生存。在第二个10年（从2010年到现在），CML治疗的主要目标从生存转移到生存，被认为是一个目标，无治疗缓解（TFR）。出现了两种现象：不超过50-60％的CML患者可能是停药的候选人，其中超过50％的患者分子复发。特定TKI脱靶副作用的增加的累积发生率与迫使在相当大比例的患者中停止或减少TKI施用以及在患者的特定设置中避免特定TKI相关。因此,治疗策略必须适应各类患者.基于最小有效剂量原则的替代策略已经过成功的测试,现在对其进行了重新评估。因为它们保证了生存和更好的生活质量，也是。从治疗疾病转向治疗患者是范式的重要变化。我们可以说我们正在进入个性化的CML治疗，考虑到病人的年龄，他们的合并症，耐受性,和具体的目标。在这种情况下，支持病人监测的新技术，比如数字PCR，必须考虑。在本次审查中，我们深入介绍了这一演变，并对CML治疗的未来前景进行了评论。
