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

• ClinicalTrials.gov Identifier: NCT02301065
• Recruitment Status: Completed
• First Posted: November 25, 2014
• Last Update Posted: July 17, 2017
• Sponsor: St. Jude Children's Research Hospital
• Collaborator: Michigan State University
• Information provided by (Responsible Party): St. Jude Children's Research Hospital

Study Description

Brief Summary:

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.

Condition or disease
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 Design

• Study Type: Observational
• Actual Enrollment: 35 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Analysis of KIR+CD56+ T Cells and FcRg-CD56+CD3- NK Cells in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients and Donors
• Actual Study Start Date: October 13, 2016
• Actual Primary Completion Date: February 6, 2017
• Actual Study Completion Date: February 6, 2017

Groups and Cohorts

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of KIR+CD45+ T-cells in stem cell recipients and donors [ Time Frame: 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 ]

   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.

2. Number of FcRg-CD56+CD3- NK cells in stem cell recipients and donors [ Time Frame: 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 ]

   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.

Secondary Outcome Measures :

1. Surface marker expression density of phenotype KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in donors and recipients [ Time Frame: 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 ]

   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.

2. Percentage of KIR+CD56+ T-cells that stain for tetramer/pentamer [ Time Frame: 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 ]

   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.

3. Change in numbers and percentages of KIR+CD56+T-cells after exposure to viral antigen in vitro and cytokine expression levels [ Time Frame: 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 ]

   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.

4. Number of FcRg-CD56+CD3- NK cells after exposure to cytomegalovirus [ Time Frame: 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 ]

   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.

Eligibility Criteria

• Ages Eligible for Study: up to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

Criteria

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

Contacts and Locations

Locations

United States, Tennessee

St. Jude Children's Research Hospital

Memphis, Tennessee, United States, 38105

Sponsors and Collaborators

St. Jude Children's Research Hospital

Michigan State University

Investigators

• Principal Investigator: Aimee Talleur, MD; St. Jude Children's Research Hospital

More Information

Additional Information:

St. Jude Children's Research Hospital 

Clinical Trials Open at St. Jude 

• Responsible Party: St. Jude Children's Research Hospital
• ClinicalTrials.gov Identifier: NCT02301065
• Other Study ID Numbers: KIRT
• First Posted: November 25, 2014
• Last Update Posted: July 17, 2017
• Last Verified: July 2017

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by St. Jude Children's Research Hospital:

Viral; Infection; Allogeneic Stem Cell Transplant

Additional relevant MeSH terms:

Hematologic Neoplasms; Neoplasms; Neoplasms by Site; Hematologic Diseases