Immunomodulation Following Transfusion

Study Overview
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Brief Summary
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This study is designed to provide information on patients' immune response after exposure to transfused blood. Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of these effects in patients who are not on chemotherapy is unknown. These effects are thought to be due largely to white blood cells present in the transfusion product. Leukofiltration and gamma-irradiation are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively. In this study, patients scheduled for cardiac surgery are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery. Studies will measure changes in antibody to HLA and in cells that regulate the immune response. The levels of sensitization and immunosuppression will be correlated to the transfusion products received.

Detailed Description
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Blood transfusions may have opposite immune effects on patients. One is sensitization. The other is immunosuppression. The magnitude of this problem in patients who are not on chemotherapy is unknown. Of patients who do receive donor blood, 50-90 percent become sensitized (make antibody) to HLA proteins present on white blood cells in the donor blood. This is an undesired effect in patients who need an organ or stem cell transplant, as it increases the risk of rejection. Another effect of receiving a blood transfusion, immunosuppression, causes a decreased immune response that compromises patients' ability to fight off infection or tumor cells. These effects - sensitization and immunosuppression - are thought to be due largely to white blood cells present in the transfusion product. Doctors order specially pretreated blood transfusions that have been depleted of white blood cells with the aim of minimizing risks in an immunocompromised patient. Leukofiltration and gamma-irradiation are the special treatments that deplete white blood cells. A combination of leukofiltration and gamma-irradiation pretreatment of donor blood is thought to deplete the white blood cells most effectively. Therefore, blood is pretreated both ways before it is given to patients who need a stem cell transplant or others who are immunosuppressed. Sometimes the pretreated leukofiltration and gamma-irradiated blood is used for regular patients who are not immunocompromised so the blood is used before it expires and not wasted. However, doctors do not know for sure whether these expensive pretreatments are really beneficial for regular patients such as those undergoing cardiac surgery and whether they would change the risk of developing sensitization or immunosuppression. In this study, patients are randomly assigned to receive blood products pretreated in one of three ways: untreated, filtered or filtered and irradiated. If their physician orders transfusions, they will receive products assigned to their group. Patients are asked to provide two blood samples during the 4 weeks after surgery. Studies will measure changes in antibody to HLA and in cells that regulate the immune response. It is unknown which treatment (leukofiltration with or without gamma-irradiation compared to no pretreatment) is most beneficial in patients who are not immunosuppressed. This study is designed to provide information on patients' immune response after exposure to transfused blood. This information may be useful to caring for patients in the future who require transfusion for cardiac surgery.

Official Title
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Immunomodulation Following Transfusion

Conditions
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Blood Component Transfusion

Intervention / Treatment
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* Biological: Standard blood components
* Biological: Leukoreduced blood components
* Biological: Leukoreduced and irradiated


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 18 year of age Scheduled for open heart surgery of cardiopulmonary bypass that involves: CABG, CABG with valve, aneurysm repair Urgent or elective surgery Exclusion Criteria: Scheduled for open heart surgery of cardiopulmonary bypass that involves: placement of a ventricular assist device, cardiac transplantation, aortic dissection repair Emergent surgery participation in other clinical research studies within 30 days of randomization. Immunosuppressive treatment. Refuse blood transfusion Disease or condition placing subject at undue risk or decision of attending doctor. Condition requiring high volume transfusion therapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Individuals who consented for study were scheduled for cardiac surgery. They were randomized to one of three arms to receive blood components prepared by different, but clinically acceptable processes. If they required transfusion from 2 days prior to surgery until 30 days post surgery they received study product. Blood samples were collected prior to surgery and at two points after surgery.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Blood components with no additional treatment | Biological: Standard blood components<br>* Transfusion, if ordered by physician, with unfiltered red blood cells and apheresis platelets<br>|
| Experimental: 2<br>Blood components leukoreduced | Biological: Leukoreduced blood components<br>* Transfusion, if ordered by a physician, of leukoreduced red blood cells and apheresis platelets<br>|
| Experimental: 3<br>Blood components leukoreduced and irradiated | Biological: Leukoreduced and irradiated<br>* Transfusion, if ordered by physician, of gamma irradiated leukoreduced red blood cells and gamma irradiated apheresis platelets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Changes in the Production of Antibody to HLA Antigens | Blood samples were collected prior to surgery and at two times after surgery. Serum was tested for the presence of IgG antibody to HLA. the results of the samples collected after surgery were compared to those in the sample collected prior to surgery. | 0 to 5 weeks after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Changes in the Number or Cytokine Profile of CD4 T Regulatory Cells or NKT Cells. Number of Participants With Changes in Numbers of Cells Producing TGFB1. Number of Participants With Changes in Secretion of Cytokines | Blood samples were collected prior to surgery and at two times after surgery. White blood cells were isolated and frozen. The thawed cells were tested for the numbers and phenotype of regulatory cells and for the production of regulatory cytokines. Results obtained from samples collected after surgery were compared to the results obtained from the sample collected prior to surgery. | 0 to 5 weeks after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Component Transfusion, Leukoreduction, HLA antibody, Immunosuppression