RH Genotype Matched RBC Transfusions (RBC)

RH Genotype Matched Red Cell Transfusions for Patients With Sickle Cell Disease

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

Study Overview

• Status: Recruiting
• Conditions: Sickle Cells Disease
• Intervention / Treatment: Biological: Red cell units that are genotype matched at the RHD and RHCE loci

Detailed Description

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 New York Blood Center. Patients will be matched with donor units whose RH genotypes predict no foreign Rh protein exposure to the patient. This will provide red cell matching at a level above the current standard of care (serologic C, E, and K matching). Patients will receive RH matched red cells for the duration of their chronic transfusion therapy or up to three years, whichever is shorter. In the pilot phase, we have determined it is feasible to identify RH matched donor units for the patient's RH genotype for every scheduled transfusion. We will now continue to show feasibility as well as determine efficacy by monitoring Rh alloantibody formation.

For subjects with a history of stroke/recurrent transient ischemic attack or other indication who require tight control of Hb S, and RH genotyped blood is not available, standard of care serologic matched blood would be administered rather than delaying transfusion and risking higher Hb S level.

For all subjects, standard of care serologic matched blood would be administered rather than delaying transfusion beyond 7 days.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Stella Chou, MD; Phone Number: 215-590-0947; Email: chous@chop.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Stella Chou, MD; Phone Number: 215-590-0947; Email: chous@chop.edu
      • Principal Investigator: Stella Chou, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects age >6 months
• Diagnosis of SCD, all genotypes
• Require a period of chronic red cell transfusion therapy
• Subject/parental/guardian permission (informed consent) and if appropriate, child assent

Exclusion Criteria:

• Rare RH genotype that would preclude identification of sufficient RBC units
• Antigen negative requirements due to alloimmunization that would preclude identification of sufficient RBC units
• Alloimmunized to D antigen
• Rh alloimmunized patients for whom providing RH genotype matched blood would expose the patient to an antigen that would not be consistent with standard of care and blood bank protocols
• Parents/guardians or subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RH genotype matched red cell transfusions; 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.	Biological: Red cell units that are genotype matched at the RHD and RHCE loci; Patients will be provided with red cell units that are C, E, and K antigen matched (standard of care for patients with SCD) and genotype matched at the RHD and RHCE loci.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the treatment efficacy by monitoring the rate of Rh alloimmunization	A primary objective is to determine whether providing RH genotype matched red cell units can reduce or prevent Rh alloimmunization.	3.5 years
Determine the feasibility of identifying sufficient RH genotype matched units	A primary objective is to determine the feasibility of identifying sufficient RH genotype matched red cells for chronically transfused patients with SCD with varied RH genotypes. Approximately 20 RHD (Rhesus D) and 20 RHCE (Rhesus CE) variants have been observed in patients with SCD and will determine whether sufficient RH genotyped units can be matched to the patient's own RH genotype.	3.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the rate of non-Rh alloimmunization	A secondary objective is to determine the rate of antibody formation outside the Rh blood group system, such as anti-Kidd or -S/s.	3.5 years

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); New York Blood Center
• Investigators: Principal Investigator: Stella Chou, MD, Children's Hospital of Philadelphia

Publications and helpful links

General Publications

• Chou ST, Jackson T, Vege S, Smith-Whitley K, Friedman DF, Westhoff CM. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors. Blood. 2013 Aug 8;122(6):1062-71. doi: 10.1182/blood-2013-03-490623. Epub 2013 May 30.
• Vichinsky EP, Earles A, Johnson RA, Hoag MS, Williams A, Lubin B. Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood. N Engl J Med. 1990 Jun 7;322(23):1617-21. doi: 10.1056/NEJM199006073222301.
• Yawn BP, Buchanan GR, Afenyi-Annan AN, Ballas SK, Hassell KL, James AH, Jordan L, Lanzkron SM, Lottenberg R, Savage WJ, Tanabe PJ, Ware RE, Murad MH, Goldsmith JC, Ortiz E, Fulwood R, Horton A, John-Sowah J. Management of sickle cell disease: summary of the 2014 evidence-based report by expert panel members. JAMA. 2014 Sep 10;312(10):1033-48. doi: 10.1001/jama.2014.10517. Erratum In: JAMA. 2014 Nov 12;312(18):1932. JAMA. 2015 Feb 17;313(7):729.
• Chou ST, Evans P, Vege S, Coleman SL, Friedman DF, Keller M, Westhoff CM. RH genotype matching for transfusion support in sickle cell disease. Blood. 2018 Sep 13;132(11):1198-1207. doi: 10.1182/blood-2018-05-851360. Epub 2018 Jul 19.
• Coleman S, Westhoff CM, Friedman DF, Chou ST. Alloimmunization in patients with sickle cell disease and underrecognition of accompanying delayed hemolytic transfusion reactions. Transfusion. 2019 Jul;59(7):2282-2291. doi: 10.1111/trf.15328. Epub 2019 Apr 25.

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2020
• Primary Completion (Estimated): April 1, 2029
• Study Completion (Estimated): October 1, 2029

Study Registration Dates

• First Submitted: November 6, 2019
• First Submitted That Met QC Criteria: November 6, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 24, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Chronic Transfusion
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 19-016565; R01HL147879 (U.S. NIH Grant/Contract); R01HL169401 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Protected Health Information (PHI) will be shared with the New York Blood Center (NYBC) to order blood for the subjects. This will be done using a secure online blood ordering system. The NYBC uses an FDA-approved HIPAA secure system called Blood Enterprise Computer System (BECS) to store patient data and results, including PHI. 3rd party computers at New York Blood Center will also store study data using study identification (ID) numbers. The purpose of having study data coded at NYBC is for specialized testing for red antigens or antibodies for which we will provide some clinical data to assist in the laboratory evaluation. To assure that the transmission of data and samples maintains confidentiality we will used study ID numbers for these samples. The master list will be maintained at the Children's Hospital of Philadelphia (CHOP). The study databases are password protected and on password protected computers at CHOP and at NYBC, that are backed up on the research servers.
• IPD Sharing Time Frame: For the duration of the study
• IPD Sharing Access Criteria: Only study team members will have access to the data.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No