Status: Funded - Open
The significance of HLA antibodies in children undergoing transplant to cure Sickle Cell Disease
Robert Nickel, MD, MSc
BACKGROUND: Sickle cell disease is an inherited blood disorder that causes pain, progressive multi-organ damage, and a decreased life expectancy. Currently, sickle cell disease can only be cured through hematopoietic stem cell transplant (HSCT).
GAP: Children with sickle cell disease can develop human leukocyte antigen (HLA) class I antibodies from red blood cell transfusions. HLA class I antibodies can cause platelet transfusion refractoriness and may represent an important immunologic biomarker, but these antibodies have never been studied in children with sickle cell disease undergoing HLA-matched HSCT.
1. Children with sickle cell disease with HLA class I antibodies will require more platelet transfusions during transplant than children without these antibodies because these antibodies will bind to HLA antigens on transfused platelets and lead to premature clearance.
2. HLA alloimmunization is a marker of a “responder” immune system, and this underlying immunology will impact stem cell engraftment.
METHODS: Serum collected pre-HSCT from children with sickle cell disease undergoing HLA-matched donor transplant will be tested for HLA class I antibodies, and these children’s transplant outcomes, including the number of platelet transfusions, will be investigated. Study involves both retrospective and prospective sample and data collection though the multicenter collaborative group Sickle Transplant Alliance for Research (STAR) www.curesicklenow.org.
IMPACT: If the project’s hypotheses are validated, then modifications to the transfusion management and/or conditioning regimen for children with HLA class I antibodies may improve outcomes for these children.
Children's National Medical Center
District of Columbia, Georgia