Kuss Bryone J, Tam Constantine S
Department of Haematology, Flinders Medical Centre, SA Pathology, Adelaide, South Australia, Australia.
Molecular Medicine and Pathology, College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia.
Intern Med J. 2017 Dec;47 Suppl 6:5-10. doi: 10.1111/imj.13680.
Chronic lymphocytic leukaemia (CLL) frequently responds to chemoimmunotherapy combining cytotoxic chemotherapy and monoclonal antibodies. However, CLL is associated with significant genetic heterogeneity, and some high-risk forms are known to be chemo-resistant and associated with early relapse.
To review the current treatment paradigm of patients with high-risk disease, in particular those with del(17p) and TP53 variants.
A 'watch and wait' approach is recommended for all patients who are asymptomatic. When symptomatic, fluorescence in situ hybridisation testing should be performed and gene sequencing considered subsequently to identify del(17p) and TP53 variants respectively. In the front-line setting, treatment within a clinical trial is the preferred option. In the relapsed or refractory setting, patients with del(17p) or TP53 aberrations should be offered treatment with a novel agent, such as ibrutinib, idelalisib-rituximab or venetoclax. However, of note, at the date of this publication venetoclax is not PBS reimbursed, and ibrutinib will not be reimbursed until 1 December 2017.
Testing for del(17p) and TP53 variants identifies high-risk CLL that requires specialist management.
慢性淋巴细胞白血病（CLL）通常对细胞毒性化疗与单克隆抗体联合的化学免疫疗法有反应。然而，CLL存在显著的基因异质性，已知一些高危形式对化疗耐药且与早期复发相关。
回顾高危疾病患者，特别是那些存在17p缺失和TP53变异患者的当前治疗模式。
对于所有无症状患者，推荐采用“观察等待”方法。出现症状时，应进行荧光原位杂交检测，随后考虑基因测序以分别识别17p缺失和TP53变异。在一线治疗中，临床试验中的治疗是首选方案。在复发或难治性情况下，对于存在17p缺失或TP53畸变的患者，应给予新型药物治疗，如伊布替尼、idelalisib-利妥昔单抗或维奈托克。然而，值得注意的是，在本出版物发布之日，维奈托克尚未获得澳大利亚药品福利计划（PBS）报销，伊布替尼在2017年12月1日前也不会报销。
检测17p缺失和TP53变异可识别需要专科管理的高危CLL。
