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

5 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 data supports the idea that Genotype-Matched Blood Transfusion for Sickle Cell Disease is an effective treatment?

The available research shows that Genotype-Matched Blood Transfusion can help reduce complications in sickle cell disease patients. One study found that patients with partial D antigens who received genotype-matched transfusions had fewer issues with anti-D antibodies, which can cause problems with blood transfusions. Another study highlighted that using genotype-matched blood can lower the risk of Rh immunization, a common issue in sickle cell patients receiving transfusions. This suggests that matching the blood more closely to the patient's genetic makeup can improve the effectiveness and safety of transfusions compared to traditional methods. ^{1 2 3 4 5}

What safety data exists for genotype-matched blood transfusion in sickle cell disease?

The safety data for genotype-matched blood transfusion in sickle cell disease suggests that RH genotype matching may reduce Rh alloimmunization, which is a common issue despite serologic Rh-matched transfusions. Studies indicate that patients with partial D antigens may benefit from RH genotype-matched transfusions to prevent anti-D formation. RH genotype matching is feasible and could optimize the use of minority donor blood, although it requires more resources and donor recruitment. High-resolution RH genotyping has shown that variant alleles contribute to Rh alloimmunization, and matching based on RH genotype could potentially reduce this risk. However, the feasibility and cost of implementing widespread RH genotyping remain challenges. ^{1 2 4 5 6}

Is the treatment D+ RH genotype matched red cell units a promising treatment for sickle cell disease?

Yes, D+ RH genotype matched red cell units are promising for sickle cell disease because they can help prevent the development of harmful antibodies during blood transfusions. This matching can improve the use of valuable blood donations, reduce the risk of immune reactions, and ensure better compatibility between donors and patients. ^{1 2 3 4 7}

Research Team

Stella Chou, MD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Variant RHD alleles and Rh immunization in patients with sickle cell disease. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Molecular characterization of GYPB and RH in donors in the American Rare Donor Program. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Challenges in providing compatible blood with Rh genotype-matching in Brazilian patients with sickle cell disease. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

RH genotype matching for transfusion support in sickle cell disease. [2022]

7. England 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. [2017]