Characteristics and Dynamics of TCR Repertoire in Patients With Hematological Malignancies After Allo-HSCT
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Study Design
Outcome Measures
Primary Outcome Measures
- 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. [3 months]
To identify the mechanisms specific for TCR repertoire dynamics and rearrangement characteristics.
Secondary Outcome Measures
- 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]
Characterize the main TCR β-chain CDR3 sequences dynamic change responsible for acute GVHD, chronic GVHD and defects in protective immunity in patients undergoing HSCT.
- Perform horizontal comparison analysis on the diversity index of T cells purified from the grafts and the patients undergoing allogeneic HSCT. [1 year]
Characterize the TCR β-chain CDR3 repertoire dynamic change responsible for acute GVHD, chronic GVHD and defects in protective immunity in patients undergoing HSCT.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Patients with AML, ALL, MDS, undergone myeloablative hematopoietic stem cell transplantation about 1 year ago.
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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.
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Patients whose residual grafts have been freezed up to now.
Exclusion Criteria:
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Patients whose grafts or residual peripheral blood mononuclear cell samples are failed to be thawed.
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Patients whose samples are failed with RNA extraction.
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Patients whose RNA sequencing are failed.
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Patients who died within 2 months after allo-HSCT.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Affiliated Hospital to Academy of Military Medical Sciences | Beijing | Beijing | China | 100071 |
Sponsors and Collaborators
- Affiliated Hospital to Academy of Military Medical Sciences
- Hangzhou ImmuQuad Biotechnologies, LLC
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 307-TCR-NGS-001