Anti-D Antibodies, Sickle Cell Disease
Conditions
Keywords
Chronic Transfusion
Brief summary
This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically transfused patients with sickle cell disease (SCD) who type D+ but have formed anti-D and are currently transfused with D- RBC (Red Blood Cell) units.
Detailed description
Red blood cell transfusion remains a critical therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in patients with SCD. Recent studies performed by Investigators and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Anti-D formation in D+ patients occurs frequently, and once identified, providing D- cells for all subsequent transfusions can be challenging. These anti-D antibodies in D+ patients suggest exposure to different or variant D protein on donor cells. Investigators will test whether transfusion of patients with anti-D with RHD genotyped matched red cells is feasible, safe and can decrease D- donor unit demand.
Interventions
BIOLOGICALD+ RH genotype matched red cell units for transfusion
Chronically transfused patients with SCD and anti-D will receive D+ RH genotyped matched red cell units for transfusion in addition to standard C, E, and K antigen matching and being hemoglobin S negative, which is the Children's Hospital of Philadelphia institutional standard of care for patients with SCD. RH genotyping of donor units will be performed by the New York Blood Center (NYBC) Immunogenetics laboratory.
Sponsors
New York Blood Center
National Heart, Lung, and Blood Institute (NHLBI)
Children's Hospital of Philadelphia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects age \> 8 years old * Diagnosis of SCD, all genotypes * Require chronic red cell transfusion therapy * History of anti-D * RH genotype predicts D+ expression
Exclusion criteria
* Rare RH genotype that would preclude sufficient RBC units * Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-D Recurrence | Through study completion and follow-up phase, an average of 10 months per participant | To determine safety of providing RH genotype match red cells to patients with a history of anti-D, we observed if anti-D reappearance occurred or evidence of hemolysis of transfused red cells. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| D+ RH Genotype Matched Red Blood Cell Transfusion Investigators will provide one red cell unit of D+ RH genotype matched RBCs at the first transfusion study visit. The remainder of units will be provided per clinical standard of care, i.e. D-, CEK-matched, and negative for all other antigens the patient is alloimmunized against. If laboratory monitoring shows no reappearance of anti-D and no signs of increased red cell hemolysis, the patient will receive one unit of D+ RH genotype matched RBCs at the 2nd transfusion study visit, and if tolerated, D+ red cell exposures will increase by one unit per study visit until all units required are D+.
D+ RH genotype matched red cell units for transfusion: Chronically transfused patients with SCD and anti-D will receive D+ RH genotyped matched red cell units for transfusion in addition to standard C, E, and K antigen matching and being hemoglobin S negative, which is the Children's Hospital of Philadelphia institutional standard of care for patients with SCD. RH genotyping of donor units will be performed by the New York Blood Center (NYBC) Immunogenetics laboratory. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | D+ RH Genotype Matched Red Blood Cell Transfusion |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 5 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 0 / 5 |
| serious Total, serious adverse events | 0 / 5 |
Outcome results
Primary
Anti-D Recurrence
To determine safety of providing RH genotype match red cells to patients with a history of anti-D, we observed if anti-D reappearance occurred or evidence of hemolysis of transfused red cells.
Time frame: Through study completion and follow-up phase, an average of 10 months per participant
Population: All participants completed all study requirements with no reappearance of anti-D.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| D+ RH Genotype Matched Red Blood Cell Transfusion | Anti-D Recurrence | Anti-D recurrence | 0 Participants |
| D+ RH Genotype Matched Red Blood Cell Transfusion | Anti-D Recurrence | No anti-D recurrence | 5 Participants |