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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.

项目总结/文摘

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.