Clinical trial NCT04156906: RHD Genotype Matched Red Cells for Anti-D
Official title: RH Genotype Matched Red Cells for Patients With Sickle Cell Disease and Anti-D
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Sickle Cell Disease
Anti-D Antibodies
Keywords: Chronic Transfusion
Lead sponsor: Children's Hospital of Philadelphia
Sponsor class: OTHER
Collaborators: name: New York Blood Center
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-11-08
Enrollment: 5
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* Subjects age \> 8 years old
* Diagnosis of SCD, all genotypes
* Require chronic red cell transfusion therapy
* History of anti-D
* RH genotype predicts D+ expression

Exclusion Criteria:

* Rare RH genotype that would preclude sufficient RBC units
* Antigen negative requirements due to alloimmunization that would preclude sufficient RBC units

Primary outcomes:
measure: Anti-D Recurrence
timeFrame: Through study completion and follow-up phase, an average of 10 months per participant
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: Children's Hospital of Philadelphia
name: Stella Chou, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.