老年急性髓系白血病患者的治疗
Treatment of older patients with AML.
作者信息
Büchner Thomas, Berdel Wolfgang E, Wörmann Bernhard, Schoch Claudia, Haferlach Torsten, Schnittger Susanne, Kern Wolfgang, Aul Carlo, Lengfelder Eva, Schumacher Andrea, Reichle Albrecht, Staib Peter, Balleisen Leopold, Eimermacher Hartmut, Grüneisen Andreas, Rasche Herbert, Sauerland Maria Cristina, Heinecke Achim, Mesters Rolf M, Serve Hubert L, Kienast Joachim, Hiddemann Wolfgang
机构信息
University Hospital, Department of Medicine, Hematology and Oncology, Albert-Schweitzer-Str. 33, D-48129 Münster, Germany.
出版信息
Crit Rev Oncol Hematol. 2005 Nov;56(2):247-59. doi: 10.1016/j.critrevonc.2004.09.010. Epub 2005 Oct 21.
Undertreatment of the older patients with AML can explain, in part, their inferior outcome when compared with that in younger patients. In analogy to the benefit of patients under the age of 60 years from high-dose AraC there are dosage related therapeutic effects in the patients over 60 years in particular for daunorubicin in the induction treatment, and for maintenance versus no maintenance in the post-remission treatment. Utilizing these effects can partly overcome the mostly unfavorable disease biology in older age AML, whereas the role of risk factors involved is not completely understood and the concept of dose-response needs to be requestioned. We recommend an adequate dosage of 60 mg/(m2day) daunorubicin for 3 days in a combination with standard dose AraC and 6-thioguanine given for induction and consolidation and followed by a prolonged monthly maintenance chemotherapy. Further improvements in supportive care may help delivering additional anti-leukemic cytotoxicity. As a novel approach, reduced toxicity preparative regimens may open up allogeneic transplantation for older patients with AML. Other new options like MDR modulators, antibody targeted therapies and tyrosine kinase inhibitors are under clinical investigation. A questionnaire study in patients with AML showed that according to patients' self-assessment intensive and prolonged treatment did not result in decreasing quality of life. This finding did not vary by age under or above 60 years. Given the actual median age in this disease being more than 60 years the adequate management of older age AML remains as the major challenge.
与年轻患者相比,老年急性髓系白血病(AML)患者治疗不足在一定程度上可以解释其较差的预后。与60岁以下患者从大剂量阿糖胞苷治疗中获益类似,60岁以上患者也存在剂量相关的治疗效果,特别是在诱导治疗中柔红霉素的使用,以及缓解后治疗中维持治疗与不进行维持治疗的差异。利用这些效应可以部分克服老年AML患者大多不利的疾病生物学特性,然而其中涉及的危险因素的作用尚未完全明确,剂量反应的概念也需要重新审视。我们建议诱导和巩固治疗时,柔红霉素剂量为60mg/(m²·天),连用3天,联合标准剂量阿糖胞苷和6-硫鸟嘌呤,随后进行延长的每月一次的维持化疗。支持治疗的进一步改善可能有助于发挥额外的抗白血病细胞毒性作用。作为一种新方法,降低毒性的预处理方案可能为老年AML患者开辟异基因移植的途径。其他新的选择,如多药耐药调节剂、抗体靶向治疗和酪氨酸激酶抑制剂正在进行临床研究。一项针对AML患者的问卷调查显示,根据患者的自我评估,强化和延长治疗并未导致生活质量下降。这一发现与年龄在60岁以下或以上无关。鉴于该疾病目前的中位年龄超过60岁,老年AML的恰当管理仍然是主要挑战。