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[成人急性白血病]

[Acute leukemia in adults].

作者信息

Eigendorff E, Hochhaus A

机构信息

Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Erlanger Allee 101, 07740, Jena, Deutschland,

出版信息

Pathologe. 2015 Sep;36(5):503-17; quiz 518-9. doi: 10.1007/s00292-015-0087-y.

Abstract

BACKGROUND

The prognosis of adult patients with acute leukemia has continuously improved over the years due to the introduction of new diagnostic and therapeutic procedures and progress in the field of supportive therapy.

METHODS

This article gives an overview of the currently available options and the clinical approach to the diagnostics and therapy of acute leukemia.

RESULTS

The standardization as well as improvements in diagnostic procedures, in particular by immunocytological and genetic procedures, allow a more rapid determination of the exact diagnosis. In addition to age and performance status of patients, an established panel of cytogenetic and molecular markers allows an individual risk stratification for selecting the most appropriate therapeutic procedure for each patient. In acute myeloid leukemia (AML) younger patients with genetically determined intermediate and poor risk status benefit from allogeneic stem cell transplantation whereas patients in the low risk group are still primarily treated with conventional induction chemotherapy with anthracycline and cytarabine. The poor prognosis of elderly patients with AML has been improved by the development of stem cell transplantation procedures with reduced intensity conditioning and for patients not suitable for stem cell transplantation, the introduction of less toxic demethylating substances allows a substantial improvement in outcome and quality of life compared to cytoreductive therapy alone. The additional role of targeted therapies in AML is still under investigation. In adult patients with acute lymphoblastic leukemia (ALL), the standard systemic therapy still consists of complex cytotoxic regimens which have been modified from pediatric protocols. Biologically and genetically determined subgroups of ALL patients as well as poor responders, who can be identified by the detection of significant molecular determined residual disease (MRD) after standard therapy, benefit from allogeneic transplantation in first remission. In patients with bcr-abl positive ALL, the implementation of first and second generation tyrosine kinase inhibitors has led to rapidly rising response rates and less toxicity. Patients with relapsed ALL may benefit from new molecular options, e.g. bispecific antibodies. Additionally, improved standardization and supportive care, particularly due to the introduction of modern antimycotic agents, increase the treatment options and improve the prognosis of patients with acute leukemia.

CONCLUSION

The improved diagnostic and therapeutic options for patients with acute leukemia require a complex management. Currently only subgroups of patients benefit from molecular targeted therapeutic strategies. Due to this increasing complexity in the management, patients with acute leukemia should be treated in academic centers and within clinical trials.

摘要

背景

由于新诊断和治疗方法的引入以及支持治疗领域的进展,成年急性白血病患者的预后多年来持续改善。

方法

本文概述了目前可用的选择以及急性白血病诊断和治疗的临床方法。

结果

诊断程序的标准化以及改进,特别是通过免疫细胞学法和遗传学方法,使得能够更快地确定确切诊断。除了患者的年龄和体能状态外,一组既定的细胞遗传学和分子标志物可用于个体风险分层,以便为每位患者选择最合适的治疗方法。在急性髓系白血病(AML)中,具有基因确定的中危和高危状态的年轻患者可从异基因干细胞移植中获益,而低危组患者仍主要接受蒽环类药物和阿糖胞苷的传统诱导化疗。通过开发强度降低的预处理干细胞移植程序,老年AML患者的不良预后得到改善;对于不适合干细胞移植的患者,与单纯减瘤治疗相比,引入毒性较小的去甲基化物质可显著改善结局和生活质量。靶向治疗在AML中的额外作用仍在研究中。在成年急性淋巴细胞白血病(ALL)患者中,标准的全身治疗仍然由从儿科方案修改而来的复杂细胞毒性方案组成。ALL患者中生物学和遗传学确定的亚组以及标准治疗后可通过检测显著分子确定的残留疾病(MRD)识别出的反应不佳者,在首次缓解时可从异基因移植中获益。在bcr-abl阳性ALL患者中,第一代和第二代酪氨酸激酶抑制剂的应用导致缓解率迅速提高且毒性降低。复发ALL患者可能从新的分子选择中获益,例如双特异性抗体。此外,标准化和支持治疗的改善,特别是由于现代抗真菌药物的引入,增加了治疗选择并改善了急性白血病患者的预后。

结论

急性白血病患者诊断和治疗选择的改善需要复杂的管理。目前只有部分患者亚组能从分子靶向治疗策略中获益。由于管理的复杂性不断增加,急性白血病患者应在学术中心并参与临床试验进行治疗。

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