Institute of Hematology "L. e A. Seragnòli", Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, S.Orsola-Malpighi Hospital, Via Massarenti 9, 40138, Bologna, Italy,
Drugs. 2014 Apr;74(6):627-43. doi: 10.1007/s40265-014-0207-7.
Chronic myeloid leukemia (CML) is a disease of the hematopoietic stem cell characterized by a median age at diagnosis of 60-65 years according to most epidemiologic registries. Prior to the tyrosine kinase inhibitor (TKI) era, older age was considered an adverse prognostic factor and was included in two of the most used scoring systems for CML, the Sokal score and the Euro score. Moreover, older age was generally considered a limitation for the use of allogeneic stem-cell transplantation, given the higher toxicity observed. After the introduction of TKIs, age lost much of its prognostic impact in patients in chronic phase (CP), and the EUTOS score, developed in patients treated with imatinib, did not identify age as a risk variable. However, most CML patients require life-long treatment; therefore, as patients age while taking a TKI, the complexity of the management of elderly patients may increase over time. To date, imatinib, the first TKI introduced, and two second-generation TKIs, nilotinib and dasatinib, have been approved in most Western countries for the first-line treatment of CML. These drugs differ in terms of efficacy, safety, and costs; therefore, knowledge of their characteristics is extremely relevant for optimal management of elderly CML patients. We reviewed the impact of age on the first-line treatment of CP CML patients in the TKI era, considering the epidemiology of the disease, the role of comorbidities, and analyzing data from population-based studies and clinical trials.
慢性髓性白血病(CML)是一种造血干细胞疾病,根据大多数流行病学登记处的数据,其诊断中位年龄为 60-65 岁。在酪氨酸激酶抑制剂(TKI)时代之前,年龄较大被认为是一个不利的预后因素,并被纳入两种最常用的 CML 评分系统,即 Sokal 评分和 Euro 评分。此外,由于观察到更高的毒性,年龄较大通常被认为是异体干细胞移植使用的限制因素。在引入 TKI 后,年龄在慢性期(CP)患者中的预后影响大大降低,在接受伊马替尼治疗的患者中开发的 EUTOS 评分并未将年龄确定为风险变量。然而,大多数 CML 患者需要终身治疗;因此,随着患者在服用 TKI 时年龄的增长,老年患者的管理复杂性可能会随着时间的推移而增加。迄今为止,伊马替尼(第一种引入的 TKI)和两种第二代 TKI,即尼洛替尼和达沙替尼,已在大多数西方国家获得批准,用于 CML 的一线治疗。这些药物在疗效、安全性和成本方面存在差异;因此,了解它们的特点对于优化老年 CML 患者的管理非常重要。我们回顾了在 TKI 时代,年龄对 CP CML 患者一线治疗的影响,同时考虑了疾病的流行病学、合并症的作用,并分析了基于人群的研究和临床试验的数据。