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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method for administering blood transfusions to individuals with sickle cell disease (SCD). The study aims to determine if more closely matching donor red blood cells to the patient's RH genotype (a specific genetic marker) can enhance treatment. This approach, called RH Genotype Matched RBC Transfusions, targets patients with SCD who require regular blood transfusions. Ideal participants have been diagnosed with any type of SCD and regularly need red blood cell transfusions. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment functions in people and to measure its effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that RH genotype matched RBC transfusions are likely to be safe for humans?

Research has shown that matching red blood cells more closely to a patient's specific RH type can reduce the risk of reactions in people with sickle cell disease (SCD). Studies have found that when patients with SCD receive blood closely matching their RH type, they experience fewer issues during transfusions. A review of 14 years of data indicates that this detailed matching of red blood cells, including RH types, helps lower complications.

Although this study is in its early stages, with limited information on long-term safety, the findings suggest that RH genotype matching might be well-tolerated. This approach improves upon standard blood matching by reducing the chances of a transfusion reaction, an unwanted response by the body.

Overall, early research supports that RH genotype-matched transfusions could be a safer option for people with sickle cell disease who need regular blood transfusions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for sickle cell disease, which typically involve regular blood transfusions matched by common antigens, RH genotype matched red cell transfusions offer a more personalized approach. This method uses red blood cells matched specifically at the RHD and RHCE genetic loci, in addition to standard antigen matching, potentially reducing the risk of alloimmunization. Researchers are excited about this treatment because it could lead to safer transfusions, minimizing immune reactions and complications for patients with sickle cell disease. By targeting the genetic compatibility more precisely, this approach may improve patient outcomes and enhance the quality of life for those receiving regular transfusions.

What evidence suggests that RH genotype matched RBC transfusions could be effective for sickle cell disease?

This trial will evaluate the effectiveness of RH genotype matched red blood cell (RBC) transfusions for patients with Sickle Cell Disease (SCD). Studies have shown that RH genotype matched RBC transfusions can be more effective than traditional methods. Research indicates that matching blood at the molecular level, such as RH genotype matching, reduces the risk of transfusion reactions compared to standard matching methods. Specifically, previous patients experienced fewer complications, like alloimmunization (when the body attacks transfused blood), with genotype matching. Evidence also suggests that this method is practical and beneficial, especially when the donor pool includes a diverse group of people, such as African-Americans. Overall, RH genotype matched transfusions offer a promising approach to improve transfusion safety for SCD patients. ^{1 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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04156893

NCT04156893 | RH Genotype Matched RBC Transfusions This is a Phase 1/2 trial in patients with Sickle Cell Disease requiring chronic red cell transfusions. RH genotyped donor units will be obtained from the ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3621633/

Molecular matching of red blood cells is superior to ... Molecular matching is superior to serological matching in sickle cell disease patients, decreasing the risk of transfusion reactions.

3. ashpublications.org ashpublications.org/blood/article/132/11/1198/39383/RH-genotype-matching-for-transfusion-support-in

RH genotype matching for transfusion support in sickle cell ... Our results suggest that prophylactic RH genetic matching for patients with SCD is feasible with a donor pool comprised primarily of African-Americans.

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1473050223002173

Effects of prophylactic red blood cell (RBC) transfusion with ... SCD patients benefit from receiving prophylactic RBC transfusions with extended antigen matching, as demonstrated by the reduction on the rates of ...

5. haematologica.org haematologica.org/article/view/haematol.2020.270546

Red cell transfusion and alloimmunization in sickle ... In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2974591/

RH genotyping in a sickle cell disease patient contributing ... Genotyping of the RH variant predicted a severe shortage of compatible RBCs for long-term transfusion support, which contributed to the decision for ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8297678/

Complete RH and Kell matching related to low ... Extended red blood cell antigen matching for transfusions in sickle cell disease: a review of a 14-year experience from a single center (CME) Transfusion.

8. ashpublications.org ashpublications.org/blood/article/145/20/2257/516076/How-I-treat-challenging-transfusion-cases-in

How I treat challenging transfusion cases in sickle cell disease With ABO/RhD matching alone, combined data in patients with SCD show an RBC alloantibody incidence rate of 1.94 antibodies per 100 RBC units ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124013065

How I treat challenging transfusion cases in sickle cell ... Transfusion of red blood cells (RBCs) can be lifesaving for individuals living with sickle cell disease (SCD).