Red Blood Cell - IMProving trAnsfusions for Chronically Transfused Recipients

Sickle cell disease (SCD) and thalassemia are genetic disorders inducing anemia of differing pathophysiology. A primary therapy for preventing certain SCD complications (e.g., stroke) and for thalassemia major is regular red blood cell (RBC) transfusion, coupled with iron chelation to prevent the complications of transfusion-induced iron overload. For patients with pediatric hematology-oncology diagnoses with chemotherapy-induced aplasia, RBC transfusion is also common, but the degree of transfusion-induced iron overload and its implications for these patients is incompletely understood. Because iron-related tissue toxicity is a major cause of morbidity and mortality in regularly transfused patients, developing strategies to minimize iron loading and iron toxicity is a key objective of this proposal (study Aim #2), stemming from the objective to optimize RBC unit characteristics that patients with SCD and thalassemia receive beyond RBC phenotype matching for Rh C, E and K antigens (study Aim #1). The study will enroll patients with SCD, thalassemia or pediatric oncologic diagnoses receiving eligible transfusion at 6 hospital sites in the United States, as well as patients with SCD at 5 hemocenters in Brazil.

Inclusion criteria

(Aim #1):

• Well-characterized transfusion-dependent form of SCD or thalassemia (including Hemoglobin E-thalassemia and sickle-beta thalassemia) on chronic simple transfusion therapy or partial manual exchange
• On a regular simple RBC transfusion schedule, including partial manual exchange (i.e., 1-3 units scheduled every 2-6 weeks and on a minimum 6-month chronic transfusion trial; for partial manual exchange, the phlebotomy must be completed before the transfusion is started without a back and forth between rounds of phlebotomy and transfusion)
• Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert & Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or enrolled in the Brazil REDS-IV-P sickle cell disease cohort and seen at any participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro)

Exclusion criteria

(Aim #1):

• Institutionalization or imprisonment
• Foster care
• Weight <11 kg

Inclusion criteria

(Aim #2):

• Either included in Aim #1 (consented patient with SCD or thalassemia) or patient with pediatric oncologic diagnosis under care in a pediatric hematology/oncology service with anemia due to chemotherapy or primary/secondary hypo-proliferative bone marrow requiring a RBC transfusion (including HSCT)
• [In domestic study only] Age ≤21 years old (many pediatric services include care of patients up to age 21, therefore the protocol will not limit by age but instead on whether they are seen in a pediatric service)
• Planned transfusion of RBC from an aliquot or unit from a single donor
• Seen at any participating domestic hub hospital (i.e., Columbia University Irving Medical Center/Morgan Stanley Children's Hospital of New York, Weill Cornell Medical Center/Komansky Children's Hospital, Boston Children's Hospital, Froedtert & Medical College of Wisconsin/Children's Wisconsin, University of California San Francisco, Benioff Children's Hospital Oakland) or at any REDS-IV-P participating Brazil hemocenter (i.e., Childrens Institute and Adult Clinics at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, HEMOAM - Amazonas, HEMOMINAS - Minas Gerais, HEMOPE -Pernambuco, and HEMORIO - Rio de Janeiro).

Exclusion criteria

(Aim #2):

• Institutionalization or imprisonment
• Foster care
• Current active auto-immune hemolytic anemia based on positive direct antiglobulin test (DAT) with laboratory evidence of hemolysis and increased transfusion requirement
• [In domestic study only] Microangiopathic hemolytic anemia
• Weight <18 kg