Understanding and predicting relapse in acute myeloid leukemia

了解和预测急性髓系白血病的复发

基本信息

批准号：
10658836
负责人：
Jerald Patrick Radich
金额：
$ 40.96万
依托单位：
FRED HUTCHINSON CANCER CENTER
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10658836
关键词：
Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Acute leukemia Address Alleles Alternative Therapies Applications Grants Biological Assay Cancer Therapy Evaluation Program Cell Line Cells Characteristics Chronic Chronic Myeloid Leukemia Clinical Clinical Research Clinical Trials Coupled Data Detection Diagnosis Diagnostic Disease Disease model Early treatment Failure Frequencies Future Gene Expression Gene Expression Profile Gene Mutation Genes Genetic study Genotype Head Homologous Transplantation Innovative Therapy Kinetics Learning Malignant Neoplasms Measurable Measurement Measures Methods Molecular Monitor Mutation Mutation Detection Myelogenous Natural History Outcome Pathway interactions Patient Selection Patients Pharmacology Study Play Prediction of Response to Therapy Procedures Publishing Recurrent disease Regimen Relapse Reproducibility Residual Neoplasm Retrospective Studies Risk Role Sampling Surrogate Markers Testing Transplantation Treatment Efficacy Work base burden of illness chronic leukemia genetic predictors genetic signature genetic testing hematopoietic cell transplantation high risk improved leukemia molecular diagnostics molecular oncology mutant next generation sequencing outcome prediction predicting response predictive marker prospective relapse patients relapse prediction relapse risk research and development response sequencing platform standard of care success targeted treatment tool treatment optimization treatment response trial design

项目摘要

PROJECT SUMMARY/ABSTRACT Relapse remains the major obstacle to cure in leukemia. Why do some patients relapse, while others are cured? The ability to predict response, and intervene with alternative therapies before frank relapse occurs, can potentially optimize therapy, and potentially change the natural history of a particular patient’s disease. We will use AML as a model disease to demonstrate the power of the detection of measurable residual disease (MRD) and gene expression signatures in predicting treatment response. For these studies we will use archival and prospective samples from U.S. Intergroup studies so that we can accurately associate genetic changes with clinical characteristics and outcomes. In Aim 1 we will develop and test a new sequencing method, duplex sequencing, which can detect a mutation at a frequency of one mutant allele in a background of a million wild type alleles. In Aim 2, we will test three gene expression signatures head to head in predicting short and long- term treatment response, and discover pathways different in the response groups that may be future targets of drug therapy. In Aim 3, we will apply the above genetic tests to the allogeneic transplant setting, to predict relapse following non-myeloablative transplantation (and hence, direct abortive therapy). Our lab has had considerable success in using similar tools in CML and ALL, and indeed, MRD detection in these diseases have evolved to a surrogate for outcome in clinical trials. We likewise believe that in AML these aims will eventually allow us to predict outcome prior to therapy, pick therapies based on likely pathways responsible for the predicted unfavorable response, then monitor MRD, changing therapy early if the kinetics of MRD clearance are suboptimal.

项目摘要/摘要复发仍然是白血病治愈的主要障碍。为什么有些患者中继，而其他患者则被治愈？在Frank继电器发生之前，可以预测反应和干预替代疗法的能力，可以有可能优化治疗，并有可能改变特定患者疾病的自然史。我们将使用AML作为模型疾病来证明检测可测量残留疾病（MRD）的力量和基因表达信号预测治疗反应。对于这些研究，我们将使用档案和来自美国组间研究的前瞻性样本，以便我们可以将遗传变化与临床特征和结果。在AIM 1中，我们将开发和测试一种新的测序方法，双工测序，可以在一百万野生的背景下以一个突变等位基因的频率检测突变键入等位基因。在AIM 2中，我们将测试三个基因表达特征，以预测短和长的长期术语治疗响应，并发现响应组的途径不同，这可能是药物疗法。在AIM 3中，我们将将上述基因检测应用于同种异体移植设置，以预测非毛囊移植后复发（因此，直接流产疗法）。我们的实验室已经在CML和ALL中使用类似工具的成功，实际上，这些疾病中的MRD检测有在临床试验中演变为替代结果。我们同样相信，在AML中，这些目标最终将允许我们在治疗前预测结果，请根据可能导致预测的可能途径选择疗法不利的反应，然后监测MRD，如果MRD清除的动力学是次优。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Multigene Measurable Residual Disease Assessment Improves Acute Myeloid Leukemia Relapse Risk Stratification in Autologous Hematopoietic Cell Transplantation.

DOI：
10.1016/j.bbmt.2016.08.014
发表时间：
2016-11
期刊：
BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
影响因子：
4.3
作者：
Mule, Matthew P.;Mannis, Gabriel N.;Wood, Brent L.;Radich, Jerald R.;Hwang, Jimmy;Ramos, Nestor R.;Andreadis, Charalambos;Damon, Lloyd;Logan, Aaron C.;Martin, Thomas G.;Hourigan, Christopher S.
通讯作者：
Hourigan, Christopher S.