Background: Sickle cell disease (SCD) is an inherited blood disorder. It results from a single genetic change (mutation) in red blood cells (RBCs). RBCs are the cells that carry oxygen to the body. In people with SCD, some RBCs are abnormal and die early. This leaves a shortage of healthy RBCs. Researchers want to learn more about how long RBCs live in the human body. Objective: To study how long RBCs live in people with and without SCD. Eligibility: People age 18 and older who either have SCD, had SCD but were cured with a bone marrow transplant, have the sickle cell trait (SCT), or are a healthy volunteer without SCD or SCT Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. Participants will have a small amount of blood drawn from a vein. In the laboratory, the blood will be mixed with a vitamin called biotin. Biotin sticks to the outside of RBCs without changing their function, shape, or overall lifetime. This process is known as biotin labeling of RBCs. The biotin labeled RBCs will be returned to the participant via vein injection. Participants will give frequent blood samples. Their RBCs will be studied to see how many biotin labeled RBCs remain over time. This shows how long the RBCs live. Participants will give blood samples until no biotin labeled RBCs can be detected. During the study visits, participants will report any major changes to their health. Participation lasts for up to 6 months.
Study Description: This study will use biotin-labeling of red blood cells (RBCs) to determine the mean potential lifespan (MPL) of RBCs in patients with sickle cell disease (SCD) compared to patients who have successfully undergone curative bone marrow transplantation (BMT, allogeneic or autologous), participants with sickle cell trait, and healthy donors without SCD. Previous studies have corroborated the MPL of healthy donor RBCs to be approximately 115 days while RBCs from patients with SCD have a much more variable but consistently shorter MPL of approximately 32 days. Allogeneic BMT is a curative therapy for the treatment of severe SCD with stable, mixed donor recipient chimerism after BMT sufficient to reverse the sickle cell phenotype by virtue of improved donor red cell survival compared to the ineffective erythropoiesis of SCD. We predict that the hematologic variables associated with red cell survival among patients with SCD vs. participants with SCT and healthy donors can be used to determine the necessary amount of corrected hemoglobin required to overcome the red cell pathology of SCD. Data generated will be used to determine the utility of performing a population study of RBC lifespan in gene therapy treated patients to ultimately target the percentage of transferred globin gene needed to reverse SCD. The data generated will refine our understanding of the degree of correction necessary to reverse the phenotype of SCD. Objectives: Primary Objective: To determine and compare red blood cell survival in patients with SCD, patients with SCD who have undergone BMT, participants with SCT, and healthy donors, and validate the association of red cell survival with known markers of increased red cell survival. Secondary Objectives: To evaluate correlation of markers of hemolysis (reticulocyte count), number of alpha globin genes, and fetal hemoglobin with RBC survival. Endpoints: Primary Endpoint: Red blood cell survival Secondary Endpoints: Relationship of red blood cell survival to hematologic parameters. Antibody detection to biotin.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
22
Autologous cells will be collected and biotin-labeled ex vivo and reinfused to measure red cell survival
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
Mean Red Blood Cells Lifespan in Participants
Mean Days of Red Blood Cells (RBC) survival in participants with Sickle Cell Disease (SCD), participants with SCD who have undergone stem cell transplant, participants with Sickle Cell Trait, and healthy volunteers. Peripheral blood samples were analyzed by flow cytometry until biotin was not detectable on RBC.
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Number of Participants With Antibody Detection
Number of participants with Antibody detection to biotin
Time frame: Baseline, 3 months, 6 months
Mean White Blood Cell Count
Mean White Blood Cell (WBC) count between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Red Blood Cell Count
Mean Red Blood Cell (RBC) Count between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Hemoglobin Value
Mean Hemoglobin (Hb) Value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Hematocrit Value
Mean Hematocrit (Hct) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Value of Mean Corpuscular Volume
Mean Value of Mean Corpuscular Volume (MCV) between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Absolute Reticulocyte Count
Mean Absolute Reticulocyte Count (ARC) between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Aspartate Aminotransferase Value
Mean Aspartate Aminotransferase (AST) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Total Bilirubin Value
Mean Total Bilirubin value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Lactate Dehydrogenase Value
Mean Lactate Dehydrogenase (LDH) value between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Adult Hemoglobin Percentage
Mean Adult Hemoglobin (HbA) percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Sickle Hemoglobin Percentage
Mean Sickle Hemoglobin (HbS) Percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
Mean Fetal Hemoglobin Percentage
Mean Fetal Hemoglobin (HbF) Percentage between Sickle Cell Disease Pre-transplantation and Sickle Cell Disease Post-Transplantation
Time frame: Sickle Cell Disease Pre-Transplantation cohort time frame is as follows: baseline, twice weekly up to week 3 then weekly up to week 22. All other cohorts, time frame is as follows: baseline, weekly up to week 4, then every other week up to week 22.
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