Laubach Jacob, Rao Arati V
Division of Medical Oncology, Duke University Medical Center, Durham, North Carolina, USA.
Oncologist. 2008 Oct;13(10):1097-108. doi: 10.1634/theoncologist.2008-0100. Epub 2008 Oct 15.
Acute myeloid leukemia (AML) accounts for approximately 80% of acute leukemias diagnosed in adults. The elderly are disproportionately affected by AML, as 35% of newly diagnosed patients are aged >or=75 and the median age at diagnosis is 67. Elderly individuals also respond less well to standard chemotherapy than do younger individuals, as reflected by lower complete remission and relapse-free survival rates in major clinical trials. A higher prevalence of comorbid conditions as well as the unique biological features of elderly AML patients account for the relatively poor response to therapy observed in this population. Compared with AML in younger individuals, for example, AML in the elderly more often emerges from a preceding myelodysplastic syndrome and is more frequently associated with poor-prognosis karyotypes such as 5q- or 7q-. The introduction of novel therapies over the past decade has already altered the treatment paradigm of elderly individuals with AML. The first of these to emerge was gemtuzumab ozogamicin. Other agents are currently under evaluation in clinical trials, including inhibitors of multidrug resistance, farnesyltransferase inhibitors, novel nucleoside analogues, and inhibitors of the FMS-like tyrosine kinase-3. This review describes the biological features of AML in the elderly and summarizes both the current and emerging strategies for the treatment of this disease in older individuals.
急性髓系白血病(AML)约占成人确诊急性白血病的80%。老年人受AML的影响尤为严重,因为35%的新确诊患者年龄≥75岁,诊断时的中位年龄为67岁。与年轻个体相比,老年人对标准化疗的反应也较差,主要临床试验中的完全缓解率和无复发生存率较低就反映了这一点。合并症的较高患病率以及老年AML患者独特的生物学特征导致该人群对治疗的反应相对较差。例如,与年轻个体的AML相比,老年AML更常由先前的骨髓增生异常综合征发展而来,并且更频繁地与预后不良的核型相关,如5q-或7q-。在过去十年中,新型疗法的引入已经改变了老年AML患者的治疗模式。首先出现的是吉妥珠单抗奥唑米星。目前其他药物正在临床试验中进行评估,包括多药耐药抑制剂、法尼基转移酶抑制剂、新型核苷类似物以及FMS样酪氨酸激酶-3抑制剂。本综述描述了老年AML的生物学特征,并总结了目前以及正在出现的针对老年患者治疗该疾病的策略。