Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment
Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment
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DOI：
10.1002/ajh.24826
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发表时间：
2017-09-01
影响因子：
12.8
通讯作者：
Hallek, Michael
中科院分区：
文献类型：
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作者：
Hallek, Michael
疾病概述：慢性淋巴细胞白血病（CLL）是西方国家最常见的白血病。该疾病通常发生在老年患者中，并且具有高度可变的临床病程。白血病转化是由特定的基因组改变引起的，这种改变损害了克隆B细胞的凋亡。诊断：通过血细胞计数、血涂片和循环B淋巴细胞的免疫表型来确定诊断，这些免疫表型可以识别携带CD 5抗原和B细胞标志物的克隆B细胞群。存在两种预后分期系统，Rai和Binet分期系统，其通过体格检查和血细胞计数建立。各种生物学和遗传学标记也具有预后价值。17号染色体短臂缺失（del（17 p））和/或TP 53基因突变可预测对现有化疗的耐药性。一个综合的预后评分（CLL-IPI）使用遗传，生物学和临床变量最近已经开发允许CLL分为非常不同的风险groups.Therapy分类：活动性或症状性疾病或先进的Binet或Rai阶段的患者需要治疗。对于身体健康的患者，氟达拉滨、环磷酰胺和利妥昔单抗的化学免疫治疗仍然是目前的标准治疗。对于不适合的患者，目前已有证据支持一线治疗的两种选择：苯丁酸氮芥联合抗CD 20抗体（obinutuzumab或利妥昔单抗或奥法木单抗）或伊曲替尼连续治疗。在复发时，如果无治疗间隔超过3年，则可以重复初始治疗。如果疾病早期复发，应使用替代药物改变治疗，如苯达莫司汀（加利妥昔单抗），阿仑单抗，来那度胺，奥法木单抗，伊曲替尼，艾代拉里斯或维奈托克。具有del（17 p）或TP 53突变的患者可以用伊鲁替尼、维奈托克或艾代拉里斯和利妥昔单抗的组合治疗。同种异体SCT可考虑在复发患者与TP 53突变或del（17 p）或患者是难治性的化学免疫治疗和新inhibitors.Future的挑战：新的代理商（伊替尼，idelalisib，venetoclax，obinutuzumab）持有的潜力，以显着改善CLL患者的结果。然而，它们的最佳使用（在组合，顺序和持续时间方面）仍然未知。因此，CLL患者应尽可能在临床试验中接受治疗。
Disease Overview: 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.Diagnosis: 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 and B-cell markers.Prognosis: 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)) and/or mutations of the TP53 gene predict resistance to available chemotherapies. A comprehensive prognostic score (CLL-IPI) using genetic, biological, and clinical variables has recently been developed allowing to classify CLL into very distinct risk groups.Therapy: Patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. For physically fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, currently available evidence supports two options for a first-line therapy: chlorambucil combined with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) or a continuous therapy with ibrutinib. At relapse, the initial treatment may be repeated, if the treatment-free interval exceeds 3 years. If the disease relapses earlier, therapy should be changed using alternative agents such as bendamustine (plus rituximab), alemtuzumab, lenalidomide, ofatumumab, ibrutinib, idelalisib, or venetoclax. Patients with a del(17p) or TP53 mutation can be treated with ibrutinib, venetoclax, 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 chemoimmunotherapy and the novel inhibitors.Future Challenges: The new agents (ibrutinib, idelalisib, venetoclax, and obinutuzumab) hold the potential to significantly improve the outcome of CLL patients. However, their optimal use (in terms of combination, sequence, and duration) remains unknown. Therefore, CLL patients should be treated in clinical trials whenever possible.