Characteristics and Dynamics of TCR Repertoire in Patients With Hematological Malignancies After Allo-HSCT

Affiliated Hospital to Academy of Military Medical Sciences

Status: Completed

Conditions: Graft Vs Host Disease; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Recurrence

Treatments: Other: Myeloablative Hematopoietic Stem Cell Transplantation

Study type: Observational

Funder types: Other

Identifiers

NCT03575767

307-TCR-NGS-001

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 12 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with AML, ALL, MDS, undergone myeloablative hematopoietic stem cell transplantation about 1 year ago.
2. 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.
3. Patients whose residual grafts have been freezed up to now.

Exclusion criteria

1. Patients whose grafts or residual peripheral blood mononuclear cell samples are failed to be thawed.
2. Patients whose samples are failed with RNA extraction.
3. Patients whose RNA sequencing are failed.
4. Patients who died within 2 months after allo-HSCT.