RHD Genotype Matching for Anti-D
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Early Phase 1 |
Detailed Description
Red blood cell transfusion remains a critical therapy for patients with sickle cell disease (SCD). A major problem is the high rate of alloimmunization (antibody formation against transfused red cells) that occurs in patients with SCD. Recent studies performed by Investigators and others demonstrate RH genetic variants in patients and donors is a major risk factor leading to Rh alloimmunization. Anti-D formation in D+ patients occurs frequently, and once identified, providing D- cells for all subsequent transfusions can be challenging. These anti-D antibodies in D+ patients suggest exposure to different or variant D protein on donor cells. Investigators will test whether transfusion of patients with anti-D with RHD genotyped matched red cells is feasible, safe and can decrease D- donor unit demand.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: D+ RH genotype matched Red Blood Cell Transfusion 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+. |
Biological: D+ RH genotype matched red cell units for transfusion
Chronically transfused patients with SCD and anti-D will receive D+ RH genotyped matched red cell units for transfusion in addition to standard C, E, and K antigen matching and being hemoglobin S negative, which is the Children's Hospital of Philadelphia institutional standard of care for patients with SCD. RH genotyping of donor units will be performed by the New York Blood Center (NYBC) Immunogenetics laboratory.
|
Outcome Measures
Primary Outcome Measures
- Feasibility and safety of providing RH genotype matched D+ RBCs to patients with SCD who type D+ but have formed anti-D [5 years]
To determine feasibility of identifying sufficient RH genotype matched units (identifying sufficient RH genotype match red cells without delays in transfusion), and safety (no anti-D reappearance or evidence of hemolysis of transfused red cells).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Subjects age > 8 years old
-
Diagnosis of SCD, all genotypes
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Require chronic red cell transfusion therapy
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History of anti-D
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RH genotype predicts D+ expression
Exclusion Criteria:
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Rare RH genotype that would preclude sufficient RBC units
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Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- Children's Hospital of Philadelphia
- New York Blood Center
Investigators
- Principal Investigator: Stella Chou, MD, Children's Hospital of Philadelphia
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- Dezan MR, Ribeiro IH, Oliveira VB, Vieira JB, Gomes FC, Franco LAM, Varuzza L, Ribeiro R, Chinoca KZ, Levi JE, Krieger JE, Pereira AC, Gualandro SFM, Rocha VG, Mendrone-Junior A, Sabino EC, Dinardo CL. RHD and RHCE genotyping by next-generation sequencing is an effective strategy to identify molecular variants within sickle cell disease patients. Blood Cells Mol Dis. 2017 Jun;65:8-15. doi: 10.1016/j.bcmd.2017.03.014. Epub 2017 Mar 31.
- 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.
- 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. Review. Erratum in: JAMA. 2014 Nov 12;312(18):1932. JAMA. 2015 Feb 17;313(7):729.
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