Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell Transplantation
循环游离 DNA 表观遗传分析用于监测造血细胞移植后移植物抗宿主病
基本信息
- 批准号:10328516
- 负责人:
- 金额:$ 65.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-13 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:ART proteinAcuteAcute Graft Versus Host DiseaseAddressAffectAllogenicBacterial InfectionsBehavior TherapyBioinformaticsBiological AssayBiopsyBloodBlood CirculationBlood TestsCaringCell DeathCellsCessation of lifeClinicalCollaborationsColonoscopyControl GroupsDNA sequencingDataDetectionDiagnosisDiagnosticEarly DiagnosisEndoscopyEngraftmentEtiologyFutureGenetic FingerprintingsGoalsHematological DiseaseHematopoietic NeoplasmsImmuneImmune System DiseasesImmune responseInjuryLeadLifeLiverMalignant - descriptorMapsMeasurementMedicalMetagenomicsMethodsMethylationModalityMonitorNon-Invasive Cancer DetectionNon-MalignantOrganOutcomePatient MonitoringPatient-Focused OutcomesPatientsPerformancePilot ProjectsPlasmaProceduresProspective StudiesProspective cohortProteinsPublic HealthRetrospective StudiesRiskSamplingSavingsSeveritiesSkinSymptomsTestingTherapeutic immunosuppressionTimeTissuesTranslationsTransplant RecipientsTransplantationVirus Diseasesaccurate diagnosisbiobankbiomarker panelbisulfite sequencingblood treatmentcell free DNAcell typeclassification algorithmclinical practicecohortdiagnostic strategydiagnostic toolearly onsetepigenetic profilinggenome-widegraft vs host diseasehematopoietic cell transplantationimprovedinnovationliver biopsymortalitynon-invasive monitornoninvasive diagnosisorgan injuryoutcome predictionpreventprognostic performanceprophylacticprotein biomarkersrecruittooltranslational studytreatment strategy
项目摘要
Allogeneic Hematopoietic Cell Transplantation (HCT) is a widely used therapy for a variety of malignant and
nonmalignant hematologic diseases. More than 8,500 patients, receive HCT transplants in the US each year.
Yet, up to 50% of patients suffer complications due to graft-versus-host disease (GVHD) in the first year after
HCT. GVHD occurs when donor immune cells attack the patient’s own tissues. GVHD can occur anywhere, with
the skin, gut and liver most frequently affected. GVHD remains one of the major barriers to a more widespread
application of allogeneic HCT.
Early diagnosis of aGVHD is critical to inform treatment decisions and prevent serious organ injury and death.
Unfortunately, few informative diagnostic approaches are available. In current clinical practice, diagnosis of
aGVHD relies almost entirely on the presence of clinical symptoms and requires confirmation via invasive biopsy
procedures, such as skin biopsy, colonoscopy, upper endoscopy or liver biopsy. HCT patients urgently need a
better alternative.
The goal of this proposal is to develop and apply a blood test to detect acute GVHD (aGVHD) and to
predict long-term HCT outcomes. This test employs genome-wide profiling of methylation marks comprised
within circulating cell-free DNA (cfDNA) in blood to trace their tissues-of-origin, and to quantify tissue-specific
injury after HCT. This concept is supported by significant pilot data.
We will perform a retrospective study of the utility of cfDNA to stratify HCT recipients with single organ aGVHD
(Aim 1), and a prospective study of the utility of cfDNA to detect the early onset of GVHD and to predict HCT
risk (Aim 2). Together these aims explore the highly innovative concept that a measurement of the tissues-of-
origin of cfDNA in plasma enables to i) detect aGVHD, ii) quantify the severity of aGVHD and determine its organ
involvement, iii) predict post-HCT mortality, and iv) predict the outcome of aGVHD treatments.
This proposal directly addresses an urgent, unmet medical need: the early and noninvasive diagnosis of aGVHD
after HCT. These studies are therefore highly translational. A highly informative, noninvasive monitoring tool may
inform new treatment modalities and transplant strategies. Recognizing the limitations of universal prophylactic
therapy against aGVHD, cfDNA assays could find future use in guiding pre-emptive treatment strategies, thereby
reducing the need for prolonged immunosuppressive therapy after transplant. Furthermore, earlier detection of
aGVHD could lead to shorter durations of therapeutic immunosuppression and improved patient outcomes.
同种异体造血细胞移植(HCT)是一种广泛应用于各种恶性和恶性肿瘤的治疗方法
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Iwijn De Vlaminck其他文献
Iwijn De Vlaminck的其他文献
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{{ truncateString('Iwijn De Vlaminck', 18)}}的其他基金
Cell-free DNA as a versatile analyte for the monitoring of sepsis
游离 DNA 作为监测脓毒症的多功能分析物
- 批准号:
10665402 - 财政年份:2023
- 资助金额:
$ 65.69万 - 项目类别:
A spatially resolved molecular atlas of acute viral myocarditis at single-cell resolution
单细胞分辨率的急性病毒性心肌炎的空间解析分子图谱
- 批准号:
10681925 - 财政年份:2023
- 资助金额:
$ 65.69万 - 项目类别:
Cell-Free DNA in Peritoneal Fluid as a Novel and Versatile Analyte for Monitoring Peritonitis
腹膜液中的游离 DNA 作为监测腹膜炎的新型多功能分析物
- 批准号:
10428638 - 财政年份:2021
- 资助金额:
$ 65.69万 - 项目类别:
Cell-Free DNA in Peritoneal Fluid as a Novel and Versatile Analyte for Monitoring Peritonitis
腹膜液中的游离 DNA 作为监测腹膜炎的新型多功能分析物
- 批准号:
10288893 - 财政年份:2021
- 资助金额:
$ 65.69万 - 项目类别:
Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell Transplantation
循环游离 DNA 表观遗传分析用于监测造血细胞移植后移植物抗宿主病
- 批准号:
10533829 - 财政年份:2020
- 资助金额:
$ 65.69万 - 项目类别:
Epigenetic Profiling of circulating cell-free DNA for the Monitoring of Graft-Versus-Host Disease after Hematopoietic Cell Transplantation
循环游离 DNA 表观遗传分析用于监测造血细胞移植后移植物抗宿主病
- 批准号:
10084808 - 财政年份:2020
- 资助金额:
$ 65.69万 - 项目类别:
Droplet-Assisted RNA targeting by single-cell sequencing to dissect the single-cell heterogeneity of RNA virus infection
通过单细胞测序进行液滴辅助 RNA 靶向分析 RNA 病毒感染的单细胞异质性
- 批准号:
9888327 - 财政年份:2019
- 资助金额:
$ 65.69万 - 项目类别:
Host-Pathogen Interactions From Measurements of Urinary Cell Free DNA in Kidney Transplantation
肾移植中尿细胞游离 DNA 测量的宿主-病原体相互作用
- 批准号:
9375180 - 财政年份:2017
- 资助金额:
$ 65.69万 - 项目类别:
Precision monitoring of kidney transplants via single-cell and single-molecule sequencing
通过单细胞和单分子测序精确监测肾移植
- 批准号:
9350514 - 财政年份:2017
- 资助金额:
$ 65.69万 - 项目类别:
Mitochondrial Cell-Free DNA as a Marker of Rejection and Damage-Associated Molecular Pattern in Organ Transplantation
线粒体游离 DNA 作为器官移植中排斥和损伤相关分子模式的标记
- 批准号:
9335715 - 财政年份:2016
- 资助金额:
$ 65.69万 - 项目类别:
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一种治疗急性移植物抗宿主病的新型小分子疗法
- 批准号:
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