Characteristics and Dynamics of TCR Repertoire in Peripheral Blood of Patients With Hematological Malignancies After Myeloablative Allogeneic Hematopoietic Stem Cell Transplantation
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Perform TCR β-chain CDR3 high-throughput sequencing and TCR repertoire analysis on T cells from the graft and the peripheral blood at the time of 1-month, 2-month after allo-HSCT.
研究概览
简要总结
Graft-versus-Host Disease (GVHD) and relapse, which is mainly due to lack of Graft-versus-Leukemia (GVL), are the most frequent and severe complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT). T cells expanded from mature T cells in the graft play a dominant role in development of GVHD and GVL early after allo-HSCT. Recent applications of high-throughput sequencing (HTS) to the T cells repertoire open a new avenue for us to look deeply into how these T cells dynamically adjust in the context of the recipient's environment.
The main goal of this research study is to set up a mathematical model based on T cell receptor (TCR) sequencing to enable prediction for the key immunologic outcomes early post-transplantation. This study will deepen the understanding of the molecular mechanisms driving the most deadly post-transplantation complications, and serve as convincing evidence upon which to choose a better donor and a more proper transplantation approach.
This observational trial will perform HTS for TCR β-chain complementarity determining region 3 (CDR3) repertoires of grafts and peripheral blood samples from recipients post-transplantation and analyze the relationship between dynamics of TCR CDR3 repertoires and clinical outcomes early post-transplantation, especially including GVHD and relapse. The investigators want to know how the antigen environment in recipients drives dynamics of mature T cells from grafts in order to use the new discovered rules to better predict and treat the disease process.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 12 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with AML, ALL, MDS, undergone myeloablative hematopoietic stem cell transplantation about 1 year ago.
- •Patients who have residual peripheral blood mononuclear cell samples freezed up to now which had been disposed at the time of about 1-month, 2-month after allo-HSCT.
- •Patients whose residual grafts have been freezed up to now.
排除标准
- •Patients whose grafts or residual peripheral blood mononuclear cell samples are failed to be thawed.
- •Patients whose samples are failed with RNA extraction.
- •Patients whose RNA sequencing are failed.
- •Patients who died within 2 months after allo-HSCT.
结局指标
主要结局
Perform TCR β-chain CDR3 high-throughput sequencing and TCR repertoire analysis on T cells from the graft and the peripheral blood at the time of 1-month, 2-month after allo-HSCT.
时间窗: 3 months
To identify the mechanisms specific for TCR repertoire dynamics and rearrangement characteristics.
次要结局
- Perform horizontal comparison analysis on the diversity index of T cells purified from the grafts and the patients undergoing allogeneic HSCT.(1 year)
- Perform longitudinal immune analysis on T cells purified from patients undergoing allogeneic HSCT who develop acute and chronic GVHD, relapse, and virus infectious complications post-transplant.(1 year)