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FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.FLT3 内部串联重复与 60 岁及以上原发性细胞遗传学正常急性髓系白血病患者的不良预后及基因和 microRNA 表达特征相关:一项癌症和白血病组 B 的研究。
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Mutations of the Wilms tumor 1 gene (WT1) in older patients with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study.老年原发性细胞遗传学正常急性髓细胞白血病患者中 Wilms 肿瘤 1 基因(WT1)的突变:癌症和白血病组 B 的一项研究。
Blood. 2010 Aug 5;116(5):788-92. doi: 10.1182/blood-2010-01-262543. Epub 2010 May 4.
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Favorable prognostic impact of NPM1 mutations in older patients with cytogenetically normal de novo acute myeloid leukemia and associated gene- and microRNA-expression signatures: a Cancer and Leukemia Group B study.核仁磷酸蛋白 1 突变对细胞遗传学正常的初发急性髓系白血病老年患者具有有利的预后影响及相关的基因和 microRNA 表达特征:一项癌症和白血病组 B 研究。
J Clin Oncol. 2010 Feb 1;28(4):596-604. doi: 10.1200/JCO.2009.25.1496. Epub 2009 Dec 21.
4
Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet.成人急性髓系白血病的诊断和治疗:代表欧洲白血病网的国际专家小组的建议。
Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30.
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FLT3 mutations have no prognostic impact in elderly patients with acute myeloid leukemia and normal karyotype.FLT3突变对老年急性髓系白血病且核型正常的患者无预后影响。
Am J Hematol. 2009 Aug;84(8):532-5. doi: 10.1002/ajh.21458.
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Structural and functional alterations of FLT3 in acute myeloid leukemia.急性髓系白血病中FLT3的结构和功能改变
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Negative impact of FLT3 abnormalities in elderly acute myeloid leukemia patients.FLT3异常对老年急性髓系白血病患者的负面影响。
Leuk Lymphoma. 2008 May;49(5):994-7. doi: 10.1080/10428190801947567.
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Acute myeloid leukaemia.急性髓系白血病
Lancet. 2006 Nov 25;368(9550):1894-907. doi: 10.1016/S0140-6736(06)69780-8.
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Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B.细胞遗传学和年龄是60岁以上接受强化治疗的急性髓系白血病患者预后的主要决定因素:来自AMLSG试验AML HD98 - B的结果
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10
Pretreatment cytogenetics add to other prognostic factors predicting complete remission and long-term outcome in patients 60 years of age or older with acute myeloid leukemia: results from Cancer and Leukemia Group B 8461.预处理细胞遗传学可补充其他预后因素,用于预测60岁及以上急性髓系白血病患者的完全缓解和长期预后:癌症与白血病B组8461研究结果
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伴有细胞遗传学正常 AML(CN-AML)和 FLT3 突变的老年患者的结局。

Outcome of older adults with cytogenetically normal AML (CN-AML) and FLT3 mutations.

机构信息

Bone Marrow Transplant Unit, Massachusetts General Hospital, Boston, MA, USA.

出版信息

Leuk Res. 2011 Dec;35(12):1611-5. doi: 10.1016/j.leukres.2011.05.032. Epub 2011 Jun 21.

DOI:10.1016/j.leukres.2011.05.032
PMID:21696826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3498766/
Abstract

AML patients under the age of 60 whose blasts harbor a FLT3 internal tandem duplication (ITD) mutation have a higher relapse rate and inferior survival compared to those without this mutation. To determine if FLT3ITD also carries a negative prognostic impact in older adults receiving therapies commonly used in this age group, we retrospectively analyzed outcomes of patients ≥60 years with CN-AML according to FLT3 mutation status. We identified 91 newly diagnosed CN-AML patients, 55 with wild-type FLT3 and 36 with FLT3ITD. Of the 91 patients, 36 received supportive care and/or experimental therapies while the remaining 55 received induction chemotherapy, followed by allogeneic SCT in 17 of these patients. Based on univariate analysis, advanced age at diagnosis was significantly associated with shorter overall survival (OS) (p<.0001) while intensive therapies were associated with improved OS (p<.0001). In a multivariate analysis that accounted for type of treatment, patient age, gender, and WBC count, FLT3ITD was significantly associated with shorter OS compared to wtFLT3 [p=.001; hazard ratio (HR)=2.23; 95% CI: 1.35-3.70]. Our data support the negative prognostic impact of FLT3ITD in older adults with CN-AML.

摘要

年龄在 60 岁以下的 AML 患者,如果其blasts 中存在 FLT3 内部串联重复(ITD)突变,则与没有这种突变的患者相比,复发率更高,生存率更低。为了确定 FLT3ITD 在接受该年龄组常用治疗的老年患者中是否也具有负预后影响,我们根据 FLT3 突变状态回顾性分析了年龄≥60 岁的 CN-AML 患者的结局。我们确定了 91 例新诊断的 CN-AML 患者,其中 55 例为野生型 FLT3,36 例为 FLT3ITD。在这 91 例患者中,36 例接受支持性治疗和/或实验性治疗,而其余 55 例接受诱导化疗,其中 17 例接受异基因 SCT。基于单因素分析,诊断时年龄较大与总生存期(OS)较短显著相关(p<.0001),而强化治疗与 OS 改善相关(p<.0001)。在多变量分析中,考虑到治疗类型、患者年龄、性别和白细胞计数,与 wtFLT3 相比,FLT3ITD 与较短的 OS 显著相关[p=.001;风险比(HR)=2.23;95%CI:1.35-3.70]。我们的数据支持 FLT3ITD 在患有 CN-AML 的老年患者中具有负预后影响。