Department I of Internal Medicine, Center for Integrated Oncology Köln Bonn, Center of Excellence on "Cellular Stress Responses in Aging-Associated Diseases", University of Cologne, Cologne, Germany.
Am J Hematol. 2015 May;90(5):446-60. doi: 10.1002/ajh.23979.
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 available chemotherapies. Comprehensive prognostic scores are currently being developed.
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 remains the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) plus a milder chemotherapy (Chlorambucil) may be applied. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds two to three years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, or idelalisib. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib or a combination of idelalisib and rituximab. An allogeneic SCT may be considered in relapsing patients with TP53 mutations or del(17p) or patients that are refractory to repeated chemoimmunotherapies. Future challenges: Several new agents (e.g., ibrutinib, idelalisib, obinutuzumab) hold the potential to improve the outcome of patients with CLL. However, their optimal use (in terms of combination, sequence, and duration) is unknown. Therefore, CLL patients should be treated in 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。这种疾病通常发生在老年患者身上，其临床表现差异较大。白血病的发生是由特定的基因组改变引起的，这些改变会损害克隆 B 细胞的凋亡。
通过血液计数、血涂片和循环 B 淋巴细胞的免疫表型分析来诊断，这些检查可以识别携带 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，这些系统是通过体格检查和血液计数来建立的。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)）预示着对现有化疗药物的耐药性。目前正在开发综合预后评分系统。
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联合化疗仍然是目前的标准治疗方法。对于身体状况不佳的患者，可以使用抗 CD20 抗体（奥滨尤妥珠单抗、利妥昔单抗或奥妥珠单抗）联合较温和的化疗（苯丁酸氮芥）进行治疗。在疾病复发时，如果无治疗间期超过 2 至 3 年，则可以重复初始治疗。如果疾病更早复发，应使用其他药物（如苯达莫司汀联合利妥昔单抗、阿仑单抗、来那度胺、奥妥珠单抗、伊布替尼或idelalisib）进行治疗。对于存在 del(17p)或 TP53 突变的患者，可以使用伊布替尼或idelalisib 联合利妥昔单抗进行治疗。对于多次化疗后复发且存在 TP53 突变或 del(17p)的患者或对多次化疗药物难治的患者，可考虑进行异基因造血干细胞移植。
一些新的药物（如伊布替尼、idelalisib、奥滨尤妥珠单抗）有可能改善 CLL 患者的预后。然而，其最佳使用方法（联合用药、用药顺序和用药时间）尚不清楚。因此，只要有可能，CLL 患者都应在临床试验中接受治疗。
