CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients

Assessment of CMV-specific T Cell Responses by Flow Cytometry With Intracellular Cytokine Staining to Predict CMV Infection Risk in Pediatric Solid Organ Transplant Recipients

CMV infection and disease remain a significant clinical challenge for pediatric solid organ transplant (SOT) recipients. Current prevention strategies are limited to prophylaxis in which antiviral medication is administered for a period of several months or preemption in which close monitoring of CMV viral load from the peripheral blood is performed and treatment is initiated when CMV is detected. Each of these strategies has risks, costs, and limitations associated with it. Recently, assays for measurement of an individual patient's CMV immunity have been developed and are clinically available. One of these is the Viracor CMV T cell Immunity Panel. This flow cytometry based assay is performed on peripheral blood and measures cytokine release in response to CMV antigen stimulation by flow cytometry. The thresholds for this assay that confer protection against CMV infection in pediatric SOT recipients are not known. Defining CMV-specific cell mediated immune response thresholds that confer protection against CMV reactivation could inform patient specific durations of antiviral prophylaxis or pre-emptive surveillance testing. Therefore, the objective of this study is to quantify CMVresponsive T lymphocyte populations by flow cytometry (Viracor CMV T cell Immunity Panel) in pediatric heart, kidney, and liver transplant recipients within the first year of transplantation and to investigate potential threshold values that correlate with protection against CMV infection (DNAemia).

Study Overview

• Status: Active, not recruiting
• Conditions: Liver Transplant Infection; Kidney Transplant Infection; CMV; Heart Transplant Infection
• Intervention / Treatment: Other: CMV T cell Immunity Assay

• Study Type: Observational
• Enrollment (Estimated): 120

Contacts and Locations

• Study Contact: Name: Daniel Dulek, MD; Phone Number: 615-322-2250; Email: daniel.dulek@vumc.org

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University Medical Center/Lucile Packard Children's Hospital Stanford
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Medical Center/Children's Hospital of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Medical Center/Lurie Children's Hospital of Chicago
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Children's Mercy Hospital
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10467
      • Albert Einstein College of Medicine/Children's Hospital at Montefiore
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center/Duke Children's Hosptial
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children'S Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center/Children's Hospital of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Pediatric patients <18 years of age listed or anticipated to undergo kidney, heart, or liver transplantation.

Description

Inclusion Criteria:

1. < 18 years of age at the time of pre-transplant enrollment
2. Potential subject is undergoing evaluation or is currently listed for isolated heart, kidney, or liver transplantation at a participating transplant center OR is anticipated to undergo living-donor kidney or liver transplantation
3. Anticipated to receive ≤ 200 days of antiviral chemoprophylaxis

Note: Subjects who are consented, enrolled, and undergo transplantation at <18 years of age will remain in the study and be followed post-transplant according to the study plan after they turn 18 years of age. Subjects will be re-consented to remain in the study at their first study visit after turning 18 years of age.

Exclusion Criteria:

I. Exclusion Criteria pre-transplant

1. Prior history of any organ transplant
2. Prior history of hematopoietic cell transplant
3. Anticipated to receive more than one organ at the time of transplant
4. Anticipated to receive > 200 days of CMV antiviral chemoprophylaxis as part of the local transplant center's standard CMV prevention protocol
5. History of underlying primary (genetic) T cell immune deficiency

II. Exclusion Criteria post-enrollment A) Removal from study due to minimal risk for CMV infection

1. CMV seronegative children >= 12 months of age will be enrolled pre-transplant but will subsequently be excluded from the study IF they receive an organ from a CMV seronegative donor (CMV D-/R-).
2. Infants <12 months will be considered seronegative regardless of their CMV IgG status (whether or not this testing was obtained by the local transplant center) UNLESS the infant has a positive pre-transplant CMV culture (from urine) or a positive pre-transplant CMV PCR (from urine, saliva, or blood). Infants <12 months of age without evidence of prior CMV infection (as defined by these preceding criteria) will be excluded from post-transplant follow up IF they receive an organ from a CMV seronegative donor due to low risk for post-transplant CMV infection. Infants <12 months of age with evidence of prior CMV infection (as defined above) will remain in the study following transplantation.

B) Removal from study due to age

a. Subjects who are enrolled at <18 years of age but are not transplanted prior to their 18th birthday will be removed from the study and will not have further pre- or post-transplant follow up.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pediatric Solid Organ Transplant (SOT) Recipients; Pediatric patients (<18 years of age) undergoing or anticipated to undergo solid organ transplantation (heart, kidney, or liver) will be prospectively enrolled with serial blood collection for CMV T cell Immunity Assay performance.	Other: CMV T cell Immunity Assay; Flow cytometry based assay quantifying IFN-gamma expression in T cells following CMV peptide stimulation (Viracor)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CMV Infection Incidence	CMV Infection as measured by CMV DNAemia or CMV disease	12 months post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of detectable CMV T cell Immunity	Viracor T cell Immunity Assay	12 months post-transplantation

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: ViraCor Laboratories
• Investigators: Principal Investigator: Daniel Dulek, MD, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2019
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 18, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Estimated): November 16, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: cmv
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases
• Other Study ID Numbers: 180947

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No