Analysis of T Cell and Natural Killer (NK) Cell in Relation to Viral Infections in Pediatric Stem Cell Transplant Patients and Donors

Analysis of KIR+CD56+ T Cells and FcRg-CD56+CD3- NK Cells in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients and Donors

Viral infections and reactivation during pediatric allogeneic hematopoietic stem cell transplantation (HSCT) are a common occurrence and significantly contribute to post-transplant morbidity and mortality. The risk is high due to prolonged periods of immune deficiency while awaiting immune reconstitution post-transplant. Current strategies to reduce complications from viral infections include prophylactic treatment, close monitoring for viral infections and prompt treatment at the first sign of symptoms or increasing viral load. However, the most definitive treatment for viral infections remains the host's cellular defenses. Improved understanding of the immune systems response to viral infections may lead to better treatment strategies.

This study is being done to explore the relationships between T-cells and NK cells (infection fighting cells) and viral infections or reactivations in young allogeneic stem cell transplant patients. The investigators will be looking at how these cells react and function in young patients receiving allogeneic stem cell transplantation, as well as in healthy stem cell donors.

Study Overview

• Status: Completed
• Conditions: Hematologic Malignancies

Detailed Description

PRIMARY OBJECTIVE:

• To explore the expansion patterns of KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in response to viral infection and reactivation in pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients.

SECONDARY OBJECTIVES:

• To describe the phenotype of KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in pediatric allogeneic HSCT patients and healthy donors.
• To describe the specificity and functional capacity of KIR+CD56+ T-cells against viral antigens in both pediatric allogeneic HSCT patients and healthy donors.
• To describe the functional capacity of FcRg-CD56+CD3- NK cells against CMV-infected cells in both pediatric allogeneic HSCT patients and healthy donors.

• Study Type: Observational
• Enrollment (Actual): 35

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The study is planned to enroll 50 pediatric allogeneic hematopoietic stem cell transplant (HSCT) patients and 50 donors. All patients/donors who meet eligibility criteria and sign the consent form will be enrolled on the study.

Description

Inclusion Criteria:

• Patients undergoing allogeneic hematopoietic stem cell transplant (HSCT) for a hematologic malignancy or a donor for a patient undergoing allogeneic hematopoietic stem cell transplant for a hematologic malignancy.
• For HSCT patients: ages birth to 21 years old; for donors: any age.
• For minors less than 18 years old, both parents must be available on St. Jude campus to provide consent. One parent/legal guardian will be acceptable if one parent is deceased, incompetent, or when the one parent present has legal responsibility for the care and custody of the child.

Exclusion Criteria:

• Patients undergoing allogeneic hematopoietic stem cell transplant for a disease other than a hematologic malignancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Stem Cell Donors; Allogeneic hematopoietic stem cell transplant (HSCT) donors. Blood samples for phenotypes research will be collected once from donors, prior to apheresis for collection of donor stem cells.
Stem Cell Recipients; Allogeneic hematopoietic stem cell transplant (HSCT) recipients. Blood samples will be drawn prior to transplantation and every two weeks, up to day 100 post-transplantation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of KIR+CD45+ T-cells in stem cell recipients and donors	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples: a baseline sample within 1 week prior to stem cell infusion and collections every 2 weeks, up to 100 days post-transplantation Summary statistics of the two cell populations, such as mean, median, range, and standard error, will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 2 weeks, up to 100 days post-transplantation
Number of FcRg-CD56+CD3- NK cells in stem cell recipients and donors	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples: a baseline sample within 1 week prior to stem cell infusion and collections every 2 weeks, up to 100 days post-transplantation Summary statistics of the two cell populations, such as mean, median, range, and standard error, will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 2 weeks, up to 100 days post-transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Surface marker expression density of phenotype KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in donors and recipients	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have two blood samples drawn: the first within 1 week prior to stem cell infusion, and the second within 1 week of 100 days post-transplantation Surface marker expression density will be calculated and summary statistics will be provided for all calculations.	Donors once within 1 week prior to stem cell donation. HSCT recipients: within 1 week prior to stem cell infusion and within 1 week of 100 days post-transplantation
Percentage of KIR+CD56+ T-cells that stain for tetramer/pentamer	Blood samples will be drawn as follows: Donors will have percentages measured once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples, a baseline sample within 1 week prior to stem cell infusion, and collections every 28 days, up to 100 days post-transplantation The specificity of KIR+CD56+T-cells will be evaluated through viral tetramer/pentamer staining.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 28 days, up to 100 days post-transplantation
Change in numbers and percentages of KIR+CD56+T-cells after exposure to viral antigen in vitro and cytokine expression levels	Blood samples will be drawn as follows: Donors will have a blood sample drawn once within 1 week prior to stem cell donation.; HSCT recipients will have serial blood samples, including a baseline sample within 1 week prior to stem cell infusion and collections every 28 days, up to 100 days post-transplantation The functional capacity of KIR+CD56+T-cells will be evaluated through proliferation and cytokine production assays. Summary statistics will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: baseline within 1 week prior to stem cell infusion and every 28 days, up to 100 days post-transplantation
Number of FcRg-CD56+CD3- NK cells after exposure to cytomegalovirus	Blood samples will be drawn as follows: Donors will have will have one blood sample drawn within 1 week prior to stem cell donation.; HSCT recipients will have two blood samples drawn: the first within 1 week prior to stem cell infusion, and the second within 1 week of 100 days post-transplantation Summary statistics of the functional capacity of FcRg-CD56+CD3- NK against CMV-infected cells will be provided.	Donors once within 1 week prior to stem cell donation. HSCT recipients: within 1 week prior to stem cell infusion and within 1 week of 100 days post-transplantation

Collaborators and Investigators

• Sponsor: St. Jude Children's Research Hospital
• Collaborators: Michigan State University

Publications and helpful links

Helpful Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2016
• Primary Completion (Actual): February 6, 2017
• Study Completion (Actual): February 6, 2017

Study Registration Dates

• First Submitted: November 18, 2014
• First Submitted That Met QC Criteria: November 21, 2014
• First Posted (Estimate): November 25, 2014

Study Record Updates

• Last Update Posted (Actual): July 17, 2017
• Last Update Submitted That Met QC Criteria: July 14, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Infection; Allogeneic Stem Cell Transplant; Viral
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: KIRT

Drug and device information, study documents

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