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急性髓系白血病的现有和新兴疗法。

Current and emerging therapies for acute myeloid leukemia.

机构信息

Department of Hematology, Medical University of Lodz, Copernicus Memorial Hospital, Lodz, Poland.

出版信息

Clin Ther. 2009;31 Pt 2:2349-70. doi: 10.1016/j.clinthera.2009.11.017.


DOI:10.1016/j.clinthera.2009.11.017
PMID:20110045
Abstract

BACKGROUND: Acute myeloid leukemia (AML) is a clonal disease characterized by the proliferation and accumulation of myeloid progenitor cells in the bone marrow, which ultimately leads to hematopoietic failure. The incidence of AML increases with age, and older patients typically have worse treatment outcomes than do younger patients. OBJECTIVE: This review is focused on current and emerging treatment strategies for nonpromyelocytic AML in patients aged <60 years. METHODS: A literature review was conducted of the PubMed database for articles published in English. Publications from 1990 through March 2009 were scrutinized, and the search was updated on August 26, 2009. The search terms used were: acute myeloid leukemia in conjunction with treatment, chemotherapy, stem cell transplantation, and immunotherapy. Clinical trials including adults with AML aged > or =19 years were selected for analysis. Conference proceedings from the previous 5 years of The American Society of Hematology, The European Hematology Association, and The American Society for Blood and Marrow Transplantation were searched manually. Additional relevant publications were obtained by reviewing the references from the chosen articles. RESULTS: Cytarabine (AraC) is the cornerstone of induction therapy and consolidation therapy for AML. A standard form of induction therapy consists of AraC (100-200 mg/m(2)), administered by a continuous infusion for 7 days, combined with an anthracycline, administered intravenously for 3 days. Consolidation therapy comprises treatment with additional courses of intensive chemotherapy after the patient has achieved a complete remission (CR), usually with higher doses of the same drugs as were used during the induction period. High-dose AraC (2-3 g/m(2)) is now a standard consolidation therapy for patients aged <60 years. Despite substantial progress in the treatment of newly diagnosed AML, 20% to 40% of patients do not achieve remission with the standard induction chemotherapy, and 50% to 70% of first CR patients are expected to relapse within 3 years. The optimum strategy at the time of relapse, or for patients with the resistant disease, remains uncertain. Allogeneic stem cell transplantation has been established as the most effective form of antileukemic therapy in patients with AML in first or subsequent remission. New drugs are being evaluated in clinical studies, including immunotoxins, monoclonal antibodies, nucleoside analogues, hypomethylating agents, farnesyltransferase inhibitors, alkylating agents, FMS-like tyrosine kinase 3 inhibitors, and multidrug-resistant modulators. However, determining the success of these treatment strategies ultimately requires well-designed clinical trials, based on stratification of the patient risk, knowledge of the individual disease, and the drug's performance status. CONCLUSIONS: Combinations of AraC and anthracyclines are still the mainstay of induction therapy, and use of high-dose AraC is now a standard consolidation therapy in AML patients aged <60 years. Although several new agents have shown promise in treating AML, it is unlikely that these agents will be curative when administered as monotherapy; it is more likely that they will be used in combination with other new agents or with conventional therapy.

摘要

背景:急性髓系白血病(AML)是一种以骨髓中髓系前体细胞增殖和积累为特征的克隆性疾病,最终导致造血功能衰竭。AML 的发病率随年龄增长而增加,老年患者的治疗效果通常比年轻患者差。 目的:本文重点介绍年龄<60 岁非早幼粒细胞性 AML 患者的当前和新兴治疗策略。 方法:对 PubMed 数据库中以英文发表的文献进行了综述。查阅了 1990 年至 2009 年 3 月的出版物,并于 2009 年 8 月 26 日进行了更新。使用的检索词为:急性髓系白血病联合治疗、化疗、干细胞移植和免疫疗法。选择分析了包括年龄≥19 岁的 AML 成人的临床试验。手工查阅了过去 5 年美国血液学会、欧洲血液学协会和美国血液和骨髓移植协会的会议记录。通过查阅所选文章的参考文献获得了其他相关出版物。 结果:阿糖胞苷(AraC)是 AML 诱导治疗和巩固治疗的基石。标准诱导治疗方案包括阿糖胞苷(100-200mg/m2),持续静脉输注 7 天,联合静脉注射蒽环类药物 3 天。巩固治疗包括在患者达到完全缓解(CR)后接受额外的强化化疗疗程,通常使用与诱导期相同的高剂量药物。目前,高剂量阿糖胞苷(2-3g/m2)已成为年龄<60 岁患者巩固治疗的标准方案。尽管在治疗新诊断的 AML 方面取得了重大进展,但仍有 20%-40%的患者无法接受标准诱导化疗缓解,50%-70%的首次 CR 患者预计在 3 年内复发。在复发时或对耐药疾病患者的最佳治疗策略仍不确定。异体干细胞移植已成为 AML 患者首次或后续缓解期最有效的抗白血病治疗形式。免疫毒素、单克隆抗体、核苷类似物、低甲基化剂、法尼酰基转移酶抑制剂、烷化剂、FMS 样酪氨酸激酶 3 抑制剂和多药耐药调节剂等新药正在临床试验中进行评估。然而,最终确定这些治疗策略的成功需要基于患者风险分层、个体疾病知识和药物表现状态的精心设计的临床试验。 结论:AraC 和蒽环类药物的联合仍然是诱导治疗的主要方法,高剂量 AraC 现在是 AML 患者巩固治疗的标准方案,年龄<60 岁。尽管一些新药物在治疗 AML 方面显示出了希望,但作为单一药物使用时,这些药物不太可能治愈;更有可能与其他新药物或常规治疗联合使用。

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