RH Genotype Matched RBC Transfusions for Sickle Cell Disease

(RBC Trial)

Overseen By Stella Chou, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

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: Up to 3 years

35 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of RH Genotype Matched RBC Transfusions for Sickle Cell Disease?

Research suggests that matching blood transfusions based on RH genotype, rather than just blood type, can help reduce the risk of developing antibodies against transfused blood in patients with sickle cell disease. This approach is particularly important for patients with altered RH alleles, which are common in this population, and can help prevent complications from transfusions. ^{1 2 3 4 5}

Is RH genotype matched RBC transfusion safe for humans?

Research suggests that RH genotype matched RBC transfusions can help reduce the risk of Rh alloimmunization (immune response against transfused blood) in patients with sickle cell disease, which is a safety concern with traditional transfusions. However, the feasibility and resources required for widespread implementation are still being evaluated, and the current cost of RH genotyping remains a limiting factor. ^{1 2 3 5 6}

How is the RH Genotype Matched RBC Transfusions treatment different from other treatments for sickle cell disease?

This treatment is unique because it involves matching red blood cell transfusions to the specific genetic makeup of the RH blood group system in patients with sickle cell disease, reducing the risk of immune reactions that can occur with traditional blood transfusions. ^{1 3 4 5 7}

What is the purpose of this trial?

To determine the feasibility and efficacy of matching donor red cells by RH genotype for a cohort of chronically transfused patients with SCD.

Research Team

Stella Chou, MD

Principal Investigator

Children's Hospital of Philadelphia

Eligibility Criteria

This trial is for individuals over 1 year old with Sickle Cell Disease who need regular blood transfusions. It's not suitable for those with rare RH genotypes, specific antigen negative requirements due to previous immune reactions, or if matching would expose them to antigens against standard care.

Inclusion Criteria

I need long-term blood transfusions.

I have been diagnosed with sickle cell disease.

I am older than 12 months.

Exclusion Criteria

I cannot receive certain blood types due to my body's previous reactions.

Antigen negative requirements due to alloimmunization that would preclude identification of sufficient RBC units

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive RH genotype matched red cell transfusions for the duration of their chronic transfusion therapy or up to three years

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring Rh alloantibody formation

3.5 years

Treatment Details

Interventions

• Red cell units that are genotype matched at the RHD and RHCE loci

Trial Overview The study tests the feasibility of using red blood cells that are matched at the RHD and RHCE genes in patients with Sickle Cell Disease receiving chronic transfusion therapy.

Participant Groups

Group I: RH genotype matched red cell transfusions Experimental Treatment 1 Intervention

Subjects will receive RH genotyped matched red cell units for transfusion in addition to standard serologic C, E, and K antigen matching and being hemoglobin S negative, which is our institutional standard of care for patients with Sickle Cell Disease.

Red cell units that are genotype matched at the RHD and RHCE loci is already approved in United States, European Union, Canada for the following indications:

Approved in United States as RH Genotype Matched RBC Transfusions for:

• Sickle Cell Disease (SCD)

Approved in European Union as Genotype-Matched Red Blood Cell Transfusions for:

• Sickle Cell Disease (SCD)
• Chronic Transfusion Therapy

Approved in Canada as RH Genotype Matched RBC Transfusions for:

• Sickle Cell Disease (SCD)

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

A three-step molecular exploration of 265 samples from blood donors and patients revealed that 54% had RHCE variant alleles, which are often responsible for transfusion issues related to altered RH antigens.

The study identified new RHCE alleles and specific RHD polymorphisms, enhancing understanding of RH antigen expression and potentially improving transfusion management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Years Review of RHCE Alleles Detected after Weak and/or Discrepant C Results in Southern France. Pedini, P., Filosa, L., Bichel, N., et al.[2022]

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 54 Brazilian sickle cell disease patients with unexpected Rh antibodies, significant genetic variation in the RH genes was identified, differing from patterns seen in African American populations.

Using RH genotyping helped guide transfusion support, allowing for better matching of Rh genotypes in donors, which could improve patient outcomes by reducing the risk of transfusion reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies. Dinardo, CL., Kelly, S., Dezan, MR., et al.[2020]

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]

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]

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]

Genotyping for RH variants is crucial in African individuals, as it can identify potential alloantibody formation to high-prevalence Rh antigens, which may be missed by traditional serologic blood typing.

In a case study of a 7-year-old boy with sickle cell disease, RH genotyping revealed a severe shortage of compatible blood for transfusions, leading to the decision for hematopoietic stem cell transplantation, highlighting the importance of genotype-based blood selection over serologic compatibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management. Fasano, RM., Monaco, A., Meier, ER., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Five-Years Review of RHCE Alleles Detected after Weak and/or Discrepant C Results in Southern France. [2022]

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

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

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

Diversity of RH and transfusion support in Brazilian sickle cell disease patients with unexplained Rh antibodies. [2020]

4. England pubmed.ncbi.nlm.nih.gov

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

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

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

6. 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]

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

RH genotyping in a sickle cell disease patient contributing to hematopoietic stem cell transplantation donor selection and management. [2022]