HHV-6-specific T-cell Reconstitution Among Children and Adolescents After Allogeneic Stem.

NCT ID: NCT06256341

Last Updated: 2024-02-13

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 53 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-03-14
• Study Completion Date: 2023-11-01

Brief Summary

Human herpesvirus 6 (HHV-6) causes only minor symptoms in healthy individuals but in immunosuppressed patients, e.g., patients after allogeneic stem cell transplantation (HSCT), HHV-6 reactivations can lead to diseases in different organ systems. HHV-6 reactivations have also been reported to be a cause for delayed engraftment, a trigger of graft-versus-host disease and a co-factor for other virus reactivations. T-lymphocytes play an important role in the control of virus reactivations. Little is known about the development of virus-specific T-cells after allogeneic HSCT.

Detailed Description

Background:

Human herpesvirus 6 (HHV-6) causes only minor symptoms in healthy individuals but in immunosuppressed patients, e.g., patients after allogeneic stem cell transplantation (HSCT), HHV-6 reactivations can lead to diseases in different organ systems. HHV-6 reactivations have also been reported to be a cause for delayed engraftment, a trigger of graft-versus-host disease and a co-factor for other virus reactivations. T-lymphocytes play an important role in the control of virus reactivations. Little is known about the development of virus-specific T-cells after allogeneic HSCT.

Objective:

The aim of this study was the description of the HHV-6 specific cellular immunity in children and adolescents after allogeneic HSCT in the context of the clinical course.

Study design and participants:

For this prospective, cross-sectional study, 28 children and adolescents after allogeneic HSCT who received follow-up support at the respective centers were included. Patients were enrolled up to 24 months after allogeneic HSCT.. Peripheral venous blood was drawn 3, 6, 9, 12, 18, and 24 months after allogeneic HSCT. Furthermore, a blood sample was taken from 25 age- and sex-matched healthy controls without any inflammatory, immunological, or infectious diseases. This study was approved by the Institutional Review Board of the Medical University Graz and patients, parents or legal guardians of patients gave written informed consent in accordance with the Declaration of Helsinki.

Methods:

3, 6, 9, 12, 18 and 24 months after allogeneic HSCT peripheral blood mononuclear cells were isolated from patient blood, stimulated with HHV-6-specific antigen (U54) and cultured for 10 days. Furthermore, a blood sample was taken from 25 age- and sex-matched healthy controls without any inflammatory, immunological, or infectious diseases.

On day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54 for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and intracytoplasmatic activation markers IL-2 (Interleukin-2), IFN-γ (Interferon-γ), TNF-α (tumor necrosis factor-α) for flow cytometric detection of virus-specific T-cells. T-cells with intracytoplasmic expression of activation markers after stimulation with the virus antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.

The virus-specific immunity of patients to HHV-6 was compared to the virus-specific immunity of children and adolescents of a control group.

Conditions

Allogeneic Stem Cell Transplantation

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

allogeneic HSCT peripheral blood

3, 6, 9, 12, 18 and 24 months after allogeneic HSCT peripheral blood mononuclear cells were isolated from patient blood, stimulated with HHV-6-specific antigen (U54) and cultured for 10 days.

Cell cultivation, Antigen testing

Intervention Type: OTHER

day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54 for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and intracytoplasmatic activation markers (IL-2, IFN-γ, TNF-α) for flow cytometric detection of virus-specific T-cells. T-cells with intracytoplasmic expression of activation markers after stimulation with the virus antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.

No more interventions in human except blood sampling, only basic research.

healthy blood

One blood sample from a age and sex matched healthy controls without any inflammatory, immunological or infectious disease was taken. mononuclear cells were isolated from patient blood, stimulated with HHV-6-specific antigen (U54) and cultured for 10 days.

Cell cultivation, Antigen testing

Intervention Type: OTHER

day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54 for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and intracytoplasmatic activation markers (IL-2, IFN-γ, TNF-α) for flow cytometric detection of virus-specific T-cells. T-cells with intracytoplasmic expression of activation markers after stimulation with the virus antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.

No more interventions in human except blood sampling, only basic research.

Interventions

Cell cultivation, Antigen testing

day 10, peripheral blood mononuclear cells were re-stimulated with the virus antigen U54 for 6 hours and, thereafter, stained for surface markers (CD3, CD4, CD8, CD56) and intracytoplasmatic activation markers (IL-2, IFN-γ, TNF-α) for flow cytometric detection of virus-specific T-cells. T-cells with intracytoplasmic expression of activation markers after stimulation with the virus antigen are HHV-6-specific T-cells. This indicated HHV-6 specific cellular immunity.

No more interventions in human except blood sampling, only basic research.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Patients who have undergone allogeneic SCT (stem cell transplantation) at one of the participating centers in the last 24 months or who will undergo allogeneic SCT during the study period (up to 3 months before the end of the study) and complete follow-up care at the respective centers

• Age> 1 year
• Written consent by participant or legal guardian

Exclusion Criteria

• severe SCT-associated complications during the study period: Rejection of the transplant ("graft failure") severe graft-versus-host disease (GVHD grade 3 or 4)
• Relapse of the (malignant) underlying disease or occurrence of another complication (e.g. secondary malignancy), which represents an indication for cytotoxic chemotherapy (or re-transplantation) during the examination period.

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Graz

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

CIRAST HHV-6

Identifier Type: -

Identifier Source: org_study_id