Abstract：
The discovery that patients suffering from chronic myeloid leukemia who obtain deep and long-lasting molecular responses upon treatment with tyrosine kinase inhibitors may maintain their disease silent for many years after therapy discontinuation launched the era of treatment-free remission as a key management goal in clinical practice. The purpose of this review on treatment-free remission is to discuss clinical advances, highlight knowledge gaps, and describe areas of research.
Patients in treatment-free remission are a minority, and it is believed that some may still retain a reservoir of leukemic stem cells; thus, whether they can be considered as truly cured is uncertain. Strengthening BCR::ABL1 inhibition increases deep molecular responses but is not sufficient to improve treatment-free remission, and we lack biomarkers to identify and specifically target residual cells with aggressive potential. Another level of complexity resides in the intra- and inter-patient clonal heterogeneity of minimal residual disease and characteristics of the bone marrow environment. Finding determinants of deep molecular responses achievement and elucidating varying biological mechanisms enabling either post-tyrosine kinase inhibitor chronic myeloid leukemia control or relapse may help develop innovative and safe therapies. In the light of the increasing prevalence of CML, targeting the residual leukemic stem cell pool is thought to be the key.
Patients in treatment-free remission are a minority, and it is believed that some may still retain a reservoir of leukemic stem cells; thus, whether they can be considered as truly cured is uncertain. Strengthening BCR::ABL1 inhibition increases deep molecular responses but is not sufficient to improve treatment-free remission, and we lack biomarkers to identify and specifically target residual cells with aggressive potential. Another level of complexity resides in the intra- and inter-patient clonal heterogeneity of minimal residual disease and characteristics of the bone marrow environment. Finding determinants of deep molecular responses achievement and elucidating varying biological mechanisms enabling either post-tyrosine kinase inhibitor chronic myeloid leukemia control or relapse may help develop innovative and safe therapies. In the light of the increasing prevalence of CML, targeting the residual leukemic stem cell pool is thought to be the key.
摘要：
目的：发现慢性髓细胞性白血病患者在接受酪氨酸激酶抑制剂治疗后获得深度和持久的分子反应，在治疗中断后可能会使他们的疾病保持多年的沉默，这是临床实践中一个关键的治疗目标。这篇关于免治疗缓解的综述的目的是讨论临床进展，突出知识差距，并描述研究领域。
结果：无治疗缓解的患者占少数，据信，一些人可能仍然保留白血病干细胞的储库；因此，他们是否可以被认为是真正治愈是不确定的。加强BCR::ABL1抑制增加深层分子反应，但不足以改善无治疗缓解，我们缺乏生物标志物来识别和特异性靶向具有侵袭潜力的残余细胞。另一个复杂性水平在于最小残留病的患者内和患者间克隆异质性以及骨髓环境的特征。发现实现深层分子反应的决定因素并阐明使酪氨酸激酶抑制剂后慢性髓性白血病控制或复发成为可能的生物学机制可能有助于开发创新和安全的疗法。鉴于CML的患病率越来越高，靶向残留的白血病干细胞池被认为是关键。
结果：无治疗缓解的患者占少数，据信，一些人可能仍然保留白血病干细胞的储库；因此，他们是否可以被认为是真正治愈是不确定的。加强BCR::ABL1抑制增加深层分子反应，但不足以改善无治疗缓解，我们缺乏生物标志物来识别和特异性靶向具有侵袭潜力的残余细胞。另一个复杂性水平在于最小残留病的患者内和患者间克隆异质性以及骨髓环境的特征。发现实现深层分子反应的决定因素并阐明使酪氨酸激酶抑制剂后慢性髓性白血病控制或复发成为可能的生物学机制可能有助于开发创新和安全的疗法。鉴于CML的患病率越来越高，靶向残留的白血病干细胞池被认为是关键。
