Department Medicine V, University of Heidelberg, Heidelberg, Germany.
European Society for Blood and Marrow Transplantation, Leiden, The Netherlands.
Blood. 2018 Aug 30;132(9):892-902. doi: 10.1182/blood-2018-01-826008. Epub 2018 Jul 11.
High-risk chronic lymphocytic leukemia (CLL) has been defined by clinical and/or genetic resistance ( abnormalities) to treatment with chemoimmunotherapy (CIT). With the availability of pathway inhibitors (PIs), such as kinase inhibitors and BCL2 antagonists, the outlook of CIT-resistant patients has dramatically improved. Here, we propose a revision of the concept of high-risk CLL, driven by abnormalities and response to treatment with PI. CLL high-risk-I, CIT-resistant is defined by clinically CIT-resistant disease with aberrations, but fully responsive to PI. This category is largely the domain of PI-based therapy, and cellular therapy (ie, allogeneic hematopoietic cell transplantation) remains an option only in selected patients with low individual procedure-related risk. In CLL high-risk-II, CIT- and PI-resistant, characterized by increasing exhaustion of pharmacological treatment possibilities, cellular therapies (including chimeric antigen receptor-engineered T cells) should be considered in patients eligible for these procedures. Moreover, molecular and cellular therapies are not mutually exclusive and could be used synergistically to exploit their full potential.
高危慢性淋巴细胞白血病（CLL）的定义是临床和/或遗传对化疗免疫治疗（CIT）有耐药性（异常）。随着通路抑制剂（PIs）的出现，如激酶抑制剂和 BCL2 拮抗剂，CIT 耐药患者的预后有了显著改善。在这里，我们提出了一个由异常和对 PI 治疗反应驱动的高危 CLL 概念的修订。CLL 高危-I，CIT 和 PI 耐药，定义为临床 CIT 耐药疾病伴异常，但对 PI 完全有反应。这一类别主要是基于 PI 的治疗领域，细胞治疗（即异基因造血细胞移植）仅在个体程序相关风险低的选定患者中仍然是一种选择。在 CLL 高危-II，CIT 和 PI 耐药，其特征是药物治疗可能性的逐渐耗尽，细胞治疗（包括嵌合抗原受体工程 T 细胞）应考虑用于符合这些程序的患者。此外，分子和细胞疗法并不相互排斥，并且可以协同使用以充分发挥其潜力。
