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

St. Jude Children's Research Hospital35 enrolled

Overview

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.

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

Conditions

Hematologic Malignancies

Outcomes

Primary Outcomes

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.

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

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

Secondary Outcomes

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.

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

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.

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

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.

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

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.