Jeon Young-Woo, Cho Seok-Goo
Department of Hematology, Catholic Blood and Marrow Transplantation Center, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Institute for Translational Research and Molecular Imaging, Catholic Institutes of Medical Science, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea.
Korean J Intern Med. 2016 May;31(3):433-43. doi: 10.3904/kjim.2015.074. Epub 2016 Apr 5.
Only 5th decade ago, chronic lymphocytic leukemia (CLL) was only recognized as disease group of presenting features like peripheral lymphocytosis, organomegaly including of splenomegaly. As understanding of disease biology and molecular diagnostic tools are getting improved gradually, characterization of variation in CLL's clinical courses was facilitated, resulting in better risk stratification and targeted treatments. Consequently multiple new targeted agents have been used in treatment of CLL, it makes improved clinical outcome. Rituximab containing chemoimmunotherapy (combination of rituximab, fludarabine, and cyclophosphamide) have shown better overall response rate and progression-free survival on fit patients' group in front-line setting, result in standard first-line therapeutic option for CLL. Furthermore, after introducing that the B-cell receptor is crucial for the evolution and progression of CLL, emerging treatments targeting highly activated surface antigens and oncogenic signaling pathways have been associated with several successes in recent decades. These include new anti-CD 20 monoclonal antibody (obinutuzumab), the bruton tyrosine kinase inhibitor (ibrutinib), the phosphatidylinositol 3-kinase inhibitor (idelalisib), and B-cell CLL/lymphoma 2 inhibitor (ABT-199 and ABT-263). So, we discuss not only general pathophysiology of CLL, but also rapidly advancing treatment strategies that are being studied or approved for treatment of CLL.
仅在50年前,慢性淋巴细胞白血病(CLL)才刚刚被确认为一种具有外周淋巴细胞增多、包括脾肿大在内的器官肿大等特征的疾病组。随着对疾病生物学的理解和分子诊断工具的逐渐改进,CLL临床病程变异的特征得以明确,从而实现了更好的风险分层和靶向治疗。因此,多种新型靶向药物已被用于CLL的治疗,改善了临床疗效。含利妥昔单抗的化疗免疫疗法(利妥昔单抗、氟达拉滨和环磷酰胺的联合使用)在一线治疗中对适合的患者组显示出更好的总缓解率和无进展生存期,成为CLL的标准一线治疗选择。此外,在引入B细胞受体对CLL的演变和进展至关重要之后,近几十年来,针对高度活化的表面抗原和致癌信号通路的新兴治疗取得了多项成功。这些包括新型抗CD20单克隆抗体(奥妥珠单抗)、布鲁顿酪氨酸激酶抑制剂(伊布替尼)、磷脂酰肌醇3激酶抑制剂(艾代拉里斯)以及B细胞淋巴瘤-2抑制剂(ABT-199和ABT-263)。因此,我们不仅讨论CLL的一般病理生理学,还讨论正在研究或已获批准用于CLL治疗的快速发展的治疗策略。