Department I of Internal Medicine, University of Cologne, Center for Integrated Oncology Köln-Bonn, Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases, Kerpener Strasse 62, Köln, Germany.
Am J Hematol. 2013 Sep;88(9):803-16. doi: 10.1002/ajh.23491.
Chronic lymphocytic leukemia (CLL) is the commonest leukemia in western countries. The disease typically occurs in elderly patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that impair apoptosis of clonal B-cells.
The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as B-cell markers.
Two prognostic staging systems exist, the Rai and Binet staging systems, which are established by physical examination and blood counts. Various biological and genetic markers also have prognostic value. Deletions of the short arm of chromosome 17 (del(17p)) predict resistance to most available therapies.
Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physical fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab represents the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody plus a milder chemotherapy (chlorambucil) is currently established as standard treatment. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds two years. If the disease relapses earlier, alternative therapies such as bendamustine alone or with rituximab, alemtuzumab, lenalidomide, or ofatumumab should be used. Patients with a del(17p) or TP53 should be considered for an allogeneic SCT.
Several new agents (e.g., ibrutinib, obinutuzumab) hold the potential to change standard of CLL treatment in the next 6-12 months. Therefore, CLL patients should be included into current clinical trials whenever possible.
慢性淋巴细胞白血病（CLL）是西方国家最常见的白血病。该疾病通常发生于老年患者，临床病程具有高度可变性。白血病转化是由特定的基因组改变引发的，这些改变会损害克隆 B 细胞的凋亡。
通过血细胞计数、血涂片和循环 B 淋巴细胞的免疫表型分析来确立诊断，这些检查可识别携带 CD5 抗原和 B 细胞标志物的克隆 B 细胞群体。
存在两种预后分期系统，即 Rai 和 Binet 分期系统，它们是通过体格检查和血细胞计数来确立的。各种生物学和遗传学标志物也具有预后价值。染色体 17 短臂缺失（del(17p)）预测对大多数可用疗法的耐药性。
有活动性或有症状的疾病或处于晚期 Binet 或 Rai 分期的患者需要治疗。对于身体状况良好的患者，氟达拉滨、环磷酰胺和利妥昔单抗的化疗免疫治疗代表当前的标准治疗。对于身体状况不佳的患者，目前已确立用抗 CD20 抗体联合较温和的化疗（苯丁酸氮芥）作为标准治疗。在复发时，如果无治疗间期超过两年，可以重复初始治疗。如果疾病更早复发，则应使用其他替代疗法，如单独使用苯达莫司汀或联合利妥昔单抗、阿仑单抗、来那度胺或奥法妥珠单抗。有 del(17p)或 TP53 的患者应考虑进行异基因 SCT。
在未来 6-12 个月内，几种新的药物（例如伊布替尼、奥妥珠单抗）有可能改变 CLL 的标准治疗方法。因此，应尽可能让 CLL 患者参与当前的临床试验。
