Highly Sensitive Chimerism Testing to Detect Early Leukemia Relapse Post-Allo-Transplantation

高灵敏嵌合测试可检测同种异体移植后早期白血病复发

基本信息

批准号：
9619598
负责人：
Sami Barna Kanaan
金额：
$ 17.36万
依托单位：
CHIMEROCYTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-21 至 2020-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9619598
关键词：
Acute Acute Lymphocytic Leukemia Acute Myelocytic Leukemia Acute leukemia Address Alleles Allogenic Biological Assay Blood Bone Marrow Cancer Diagnostics Cells Chimerism Clinical Collaborations DNA Detection Detection of Minimal Residual Disease Diagnostics Research Differentiation Antigens Disease Disease Marker Disease remission Dysmyelopoietic Syndromes Early identification Engineering Engraftment FDA approved Foundations Frequencies GSTT1 gene Genetic Genetic Polymorphism Genotype Goals Gold HLA Antigens Hematopoietic Stem Cell Transplantation Heterogeneity Immunotherapy In Vitro Laboratories Laboratory Research Legal patent Malignant Neoplasms Methods Microchimerism Monitor Outcome Patient risk Patients Phase Physicians Polymerase Chain Reaction Population Predictive Value Pregnancy Probability Relapse Reporting Residual Neoplasm Resistance Sampling Scientist Sensitivity and Specificity Short Tandem Repeat Source Specificity Subcategory Surrogate Markers Techniques Technology Testing Therapeutic Time Transplantation assay development base chemotherapy clinical practice high risk improved leukemia medical attention new technology prevent relapse patients relapse prediction relapse risk research clinical testing screening standard of care success

项目摘要

ABST RACT Patients with acute blood malignancies who undergo allogeneic hematopoietic stem cell transplantation (HSCT) are monitored for minimal residual disease (MRD) as predictive of relapse. Increasing mixed chimerism (reemerging recipient cells) correlates with reappearance of underlying disease by association with MRD. Genetic and immunophenotypic heterogeneity of these malignancies often prevents establishing reliable MRD markers, in which case donor-vs.-recipient chimerism testing becomes the best option as a surrogate marker for MRD. At present, the widely used “gold standard” in chimerism analysis is techniques characterizing short tandem repeats (STR) with a limit-of-detection ≥ 1:100, thus unsuitable as a strategy for early relapse detection. New technologies to predict relapse post-HSCT are critical to provide rapid and individualized therapeutic assessment. Chimerocyte, Inc. is developing the Microchimerism Panel, composed of polymorphism-specific primers and fluorogenic probes to detect and quantify non-shared polymorphisms with limit-of-detection several orders of magnitude lower than currently available tests, detecting up to 1 cell equivalent per 105 background cells. To increase the probability of having an informative marker, Chimerocyte aims at developing additional highly-sensitive polymorphism-specific assays thus expanding the panel. Furthermore, we hypothesize that by sensitively monitoring chimerism using our technology, imminent relapse will be predicted with superior accuracy compared to clinical standard-of-care. We propose to test the Microchimerism Panel on post-transplant samples from 180 leukemia patients for its ability to differentiate relapse vs. sustained remission. Our collaborators have previously collected samples from regular intervals post-transplant. Results will be compared to clinical standard- of-care chimerism testing to demonstrate the ability of Chimerocyte’s Microchimerism panel in rapid high-risk patient identification. We anticipate a successful outcome that will significantly benefit cancer diagnostics and ther apy.

抽象的接受异基因造血干细胞移植（HSCT）的急性血液恶性肿瘤患者监测微小残留病（MRD）作为复发的预测。（重新出现的受体细胞）与 MRD 相关的潜在疾病的复发相关。这些恶性肿瘤的遗传和免疫表型异质性常常妨碍建立可靠的 MRD 标记，在这种情况下，供体与受体嵌合测试成为替代标记的最佳选择目前，嵌合体分析中广泛使用的“黄金标准”是表征短链的技术。串联重复序列 (STR) 的检测限≥ 1:100，因此不适合作为早期复发检测的策略。预测 HSCT 后复发的新技术对于提供快速和个体化的治疗至关重要 Chimer Bathroom, Inc. 正在开发由多态性特异性组成的微嵌合面板。引物和荧光探针可检测和定量具有多个检测限的非共享多态性比当前可用的测试低几个数量级，每 105 个背景检测多达 1 个细胞当量为了增加获得信息标记的可能性，嵌合细胞旨在开发额外的细胞。高灵敏度的多态性特异性检测从而扩大了检测范围。使用我们的技术敏感地监测嵌合现象，可以非常准确地预测即将发生的复发与临床护理标准相比，我们建议在移植后样本上测试微嵌合组。我们的合作者对 180 名白血病患者进行了区分复发与持续缓解的能力。先前从移植后定期收集的样本将与临床标准进行比较。护理嵌合测试，以证明嵌合细胞微嵌合小组在快速高风险中的能力我们预计一个成功的结果将显着有益于癌症诊断和治疗。 apy。