Clinical trial NCT02301065: Analysis of T Cell and Natural Killer (NK) Cell in Relation to Viral Infections in Pediatric Stem Cell Transplant Patients and Donors
Official title: Analysis of KIR+CD56+ T Cells and FcRg-CD56+CD3- NK Cells in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Patients and Donors
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematologic Malignancies
Keywords: Viral
Infection
Allogeneic Stem Cell Transplant
Lead sponsor: St. Jude Children's Research Hospital
Sponsor class: OTHER
Collaborators: name: Michigan State University
First posted: 2014-11-25
Enrollment: 35
Sex: ALL
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility 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

Primary outcomes:
measure: Percentage of KIR+CD45+ T-cells in stem cell recipients and donors
timeFrame: 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
measure: Number of FcRg-CD56+CD3- NK cells in stem cell recipients and donors
timeFrame: 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 outcomes:
measure: Surface marker expression density of phenotype KIR+CD56+ T-cells and FcRg-CD56+CD3- NK cells in donors and recipients
timeFrame: 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
measure: Percentage of KIR+CD56+ T-cells that stain for tetramer/pentamer
timeFrame: 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
measure: Change in numbers and percentages of KIR+CD56+T-cells after exposure to viral antigen in vitro and cytokine expression levels
timeFrame: 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
measure: Number of FcRg-CD56+CD3- NK cells after exposure to cytomegalovirus
timeFrame: 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
Other outcomes:
Locations:
city: Memphis
country: United States
facility: St. Jude Children's Research Hospital
state: Tennessee
Study officials:
affiliation: St. Jude Children's Research Hospital
name: Aimee Talleur, MD
role: PRINCIPAL_INVESTIGATOR
References: