CMV T Cell Immunity in Pediatric Solid Organ Transplant Recipients

Study Overview
=================
Brief Summary
-----------------
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).

Official Title
-----------------
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

Conditions
-----------------
CMV, Heart Transplant Infection, Kidney Transplant Infection, Liver Transplant Infection

Intervention / Treatment
-----------------
* Other: CMV T cell Immunity Assay


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: < 18 years of age at the time of pre-transplant enrollment 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 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 Prior history of any organ transplant Prior history of hematopoietic cell transplant Anticipated to receive more than one organ at the time of transplant Anticipated to receive > 200 days of CMV antiviral chemoprophylaxis as part of the local transplant center's standard CMV prevention protocol 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 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-). 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.

Ages Eligible for Study
-----------------
Minimum Age: 0 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric Solid Organ Transplant (SOT) Recipients<br>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<br>* Flow cytometry based assay quantifying IFN-gamma expression in T cells following CMV peptide stimulation (Viracor)<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cmv