Genotype-Matched Blood Transfusion for Sickle Cell Disease

Overseen By Stella Chou, MD

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: Children's Hospital of Philadelphia

Disqualifiers: Rare RH genotype, Alloimmunization, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 10 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering blood transfusions to individuals with sickle cell disease (SCD). It aims to match transfusions more closely to the patient's unique blood type to prevent complications. The trial seeks to determine if using D+ RH genotype matched red cell units (a specific type of blood transfusion) is safe and effective for those who typically require D- blood due to past reactions. Suitable candidates have SCD, require regular transfusions, and have experienced blood reactions previously. As an Early Phase 1 trial, this research focuses on understanding how this new transfusion method works in people, offering participants the opportunity to be among the first to receive this innovative treatment.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that this genotype-matched blood transfusion is safe for sickle cell disease patients?

Research has shown that using specially matched D+ red blood cells (RBCs) is generally safe for patients with sickle cell disease who have previously developed anti-D antibodies. Studies have found that these matched blood units allow patients to receive D+ blood again without major issues.

In previous research, patients who received these genotype-matched D+ RBCs did not experience a return of anti-D antibodies. There were also no significant reports of increased breakdown of red blood cells after the transfusions. These findings suggest that this treatment is well-tolerated and safe for people in similar situations.

Although this treatment is still under study, early results are promising and indicate that the blood transfusions can be done safely. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for sickle cell disease?

Unlike the standard blood transfusions for sickle cell disease, which typically involve using D- and antigen-matched red blood cells, this new approach uses D+ RH genotype matched red cell units. This method is unique because it matches the red blood cells more closely to the patient's genotype, potentially reducing the risk of alloimmunization and complications from transfusions. Researchers are excited about this treatment as it could lead to safer transfusions and better outcomes for patients by minimizing adverse reactions and improving compatibility.

What evidence suggests that D+ RH genotype matched red cell units might be an effective treatment for sickle cell disease?

Research has shown that matching the RH genotype for blood transfusions can reduce complications in people with sickle cell disease (SCD). This trial will provide participants with D+ RH genotype matched red blood cells, aligning the genetic makeup of the blood donor with the patient. This method can lower the risk of the body reacting against the transfused blood, a problem known as alloimmunization, where the body attacks the new blood. Studies have found that matching certain proteins on red blood cells, such as E, C, and K, significantly lowers this risk. Using D+ RH genotype matched red blood cells could make transfusions safer and more effective for SCD patients by reducing these reactions. ^{2 6 7 8 9}

Who Is on the Research Team?

Stella Chou, MD

Principal Investigator

Children's Hospital of Philadelphia

Are You a Good Fit for This Trial?

This trial is for people over 8 years old with sickle cell disease who need regular blood transfusions and have developed anti-D antibodies. They must have an RH genotype that suggests D+ expression. Those with rare RH genotypes or other immune responses preventing enough safe RBC units are excluded.

Inclusion Criteria

I have been diagnosed with sickle cell disease.

I am older than 8 years.

History of anti-D

Exclusion Criteria

My blood type is very rare, making it hard to find enough blood for transfusions.

I need specific blood types for transfusions due to immune reactions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive D+ RH genotype matched RBCs at the first transfusion study visit, with subsequent units provided per clinical standard of care

10 months

Multiple visits as per clinical standard of care

Follow-up

Participants are monitored for safety and effectiveness after treatment, specifically for anti-D reappearance and hemolysis

10 months

What Are the Treatments Tested in This Trial?

Interventions

• D+ RH genotype matched red cell units

Trial Overview The study tests the safety of giving chronically transfused sickle cell patients, who are D+ and have anti-D antibodies, red blood cells matched to their RH genotype instead of the usual D- units they receive.

How Is the Trial Designed?

Group I: D+ RH genotype matched Red Blood Cell Transfusion Experimental Treatment 1 Intervention

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 is already approved in United States, Canada, European Union for the following indications:

Approved in United States as RH genotype matched D+ Red Blood Cells for:

• Sickle Cell Disease

Approved in Canada as RH genotype matched D+ Red Blood Cells for:

• Sickle Cell Disease

Approved in European Union as RH genotype matched D+ Red Blood Cells for:

• Sickle Cell Disease

Who Is Running the Clinical Trial?

Children's Hospital of Philadelphia

Lead Sponsor

Trials

749

Recruited

11,400,000+

New York Blood Center

Collaborator

Trials

25

Recruited

28,400+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 182 patients with sickle cell disease, 58% of chronically transfused and 15% of episodically transfused patients developed red blood cell (RBC) alloimmunization, highlighting a significant complication of RBC transfusions.

The study found that altered Rh alleles in both patients and African American donors contributed to Rh alloimmunization, suggesting that high-resolution Rh genotyping could be a potential strategy to reduce this complication in future transfusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Chou, ST., Jackson, T., Vege, S., et al.[2022]

Rh genotype-matching for blood transfusions in Brazilian patients with sickle cell disease (SCD) is feasible, with 47.6% of patients able to meet their transfusion requests, but 52.4% faced challenges due to insufficient donor availability.

The study identified a lack of specific Rh genotypes in the donor population, particularly those associated with high prevalence antigens hrB and hrS, highlighting the need for targeted recruitment of African-Brazilian donors to improve transfusion compatibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges in providing compatible blood with Rh genotype-matching in Brazilian patients with sickle cell disease. Santos, TD., Macedo, MD., Menegati, SFP., et al.[2020]

Molecular matching of red blood cells (RBCs) for sickle cell disease (SCD) patients in Brazil has significantly reduced the rates of alloimmunization and improved clinical outcomes, including increased hemoglobin levels and better RBC survival.

Despite these advancements, challenges remain in providing antigen-matched transfusions due to issues like donor-recipient antigen discrepancies and the complexity of fulfilling transfusion requests.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimized Antigen-Matched in Sickle Cell Disease Patients: Chances and Challenges in Molecular Times - the Brazilian Way. Castilho, L., Dinardo, CL.[2022]

In a study of 690 D+ individuals with sickle cell disease, 48 developed anti-D antibodies, particularly those with partial D variants, indicating a higher risk of immunization despite receiving Rh-matched transfusions.

Patients with partial D may benefit from receiving D- or RH genotype-matched transfusions to prevent the formation of anti-D antibodies, which could improve transfusion outcomes and reduce the need for D- units.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variant RHD alleles and Rh immunization in patients with sickle cell disease. Takasaki, K., Friedman, DF., Uter, S., et al.[2023]

In a study of 130 sickle cell disease patients, 9.2% were found to carry DIIIa and DAR alleles, which can lead to unexpected antibody development against RhD despite being classified as RhD+.

The results indicate that genotyping for DIIIa and DAR alleles in SCD patients could help prevent alloimmunization during chronic transfusions, enhancing patient safety and treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High frequency of partial DIIIa and DAR alleles found in sickle cell disease patients suggests increased risk of alloimmunization to RhD. Castilho, L., Rios, M., Rodrigues, A., et al.[2017]

Rh alloimmunization is a significant issue for patients with sickle cell disease (SCD), and altered RH alleles in both patients and African American donors contribute to this problem, with about one-third of cases linked to these genetic factors.

Matching patients with donors based on RH genotype could reduce Rh alloimmunization, but it would require a larger number of African American donors compared to traditional serologic matching, highlighting the need for targeted donor recruitment to maintain an adequate blood supply.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RH genotype matching for transfusion support in sickle cell disease. Chou, ST., Evans, P., Vege, S., et al.[2022]

Genotyping donors for specific Rh phenotypes, such as U- and high-prevalence Rh antigens, is crucial for safely transfusing patients with sickle cell disease (SCD) to prevent Rh sensitization and ensure compatibility.

A study identified twelve different Rh backgrounds among eighteen donors with hr(B) or hr(S) phenotypes, highlighting the complexity of matching donors to patients and the importance of Rh genotyping to reduce the risk of alloimmunization in SCD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular characterization of GYPB and RH in donors in the American Rare Donor Program. Vege, S., Westhoff, CM.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39172743/

Genotyped RhD+ red cells for D-positive patients with sickle ... RH genotyping of D-positive units for transfusion may improve use and allocation of valuable Black donor units and reduce demand for Rh-negative ...

2. ashpublications.org ashpublications.org/blood/article/120/3/528/30463/Red-blood-cell-alloimmunization-in-sickle-cell

Red blood cell alloimmunization in sickle cell disease Matching for E, C, and K reduced the rate of alloimmunization in chronically transfused SCD patients from 3% to 0.5% per unit19 and is now the standard of care ...

3. aob.amegroups.org aob.amegroups.org/article/view/7265/html

RH genetic variation and the impact for typing and ... Conclusions: This work presents the genetics and serology of the RH blood group system that can lead to antigen discrepancies and alloimmunization due to ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11427715/

A Case Report of Red Blood Cell Alloimmunization and ... A delayed hemolytic transfusion reaction (DHTR) is a potential complication for patients with sickle cell disease (SCD) who develop red blood cell (RBC) ...

5. blutspende-srk.ch blutspende-srk.ch/sites/default/files/donwloads/2024-07/RH%20genotype%20matching%20for%20transfusion%20support%20in%20sickle%20cell%20disease_engl.pdf

RH genotype matching for transfusion support in sickle cell ... Molecular blood typing augments serologic testing and allows for enhanced matching of red blood cells for transfusion in patients with sickle cell disease.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04156906

RHD Genotype Matched Red Cells for Anti-D 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 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124022481

Genotyped RhD+ red cells for D-positive patients with ... RHD genotyping enables D-positive patients with sickle cell disease and history of anti-D to return to D-positive blood transfusion.

8. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04156906/rhd-genotype-matching-for-anti-d

RHD Genotype Matched Red Cells for Anti-D This is a pilot study to evaluate the feasibility and safety of providing RH genotype matched D+ Red Blood Cells (RBCs) to chronically ...

9. ashpublications.org ashpublications.org/blood/article/144/19/1982/525837/Are-D-units-safe-for-D-patients-with-anti-D

Are D + units safe for D + patients with anti-D? Genotype-matched RBC units will play a key role in reducing the burden on Rh− blood supplies and providing the best-matched unit to our patients ...