Pediatric Cancer, Sickle Cell Disease, Thalassemia
Conditions
Keywords
Transfusion, Red Blood Cell, Sickle Cell Disease, Thalassemia, Pediatric, Oncology, RBC survival, Genetic, Non-genetic, Observational, Blood donor
Brief summary
Red Blood Cell - IMProving trAnsfusions for Chronically Transfused recipients (RBC-IMPACT) is an observational cohort study to assess donor, component, and recipient factors that contribute to RBC efficacy in chronically and episodically transfused patients. The objective of the study is to determine how specific genetic and non-genetic factors in donors and recipients may impact RBC survival after transfusion - in short, what factors on both the donor and recipient side may improve the efficacy of the transfusion.
Detailed description
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.
Interventions
BIOLOGICALRed Blood Cell (RBC) Transfusion
Simple RBC transfusion or partial manual exchange
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Westat
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Hemoglobin A or Hemoglobin Level per day (RBC Survival) | Baseline (immediately pre-) to post-transfusion over 2 years | Change in hemoglobin A or hemoglobin level per day in between subsequent transfusion episodes, for sickle cell disease and thalassemia cohorts, respectively |
| Change in Serum Iron Level | Baseline (immediately before) and 2-hours after transfusion | For all groups participating, change in serum iron measured from immediately prior to 2 hours post-transfusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemolysis Parameter Increment | Baseline (immediately pre-) to post-transfusion or 2-hours post-transfusion, over 2 years | Includes serum iron, indirect bilirubin, or plasma free hemoglobin |
| Hemoglobin Increment | Baseline (immediately pre-) to post-transfusion, over 2 years | Hemoglobin increment \[defined as Hb/HbA(post-transfusion)visit(i) - Hb/HbA(pre-transfusion)visit(i)\] is associated with RBC survival |
| Hepcidin Level | Baseline (immediately before) to 2 hours after transfusion | Hepcidin level at time of transfusion is a predictor of change in iron parameters (i.e., transferrin saturation, serum iron) following transfusion |
| Non-Transferrin-Bound Iron (NTBI) Level | Baseline (immediately before) to 2 hours after transfusion | NTBI levels in patients with pediatric oncologic diagnoses with aplasia are elevated at baseline and increase following transfusion |
| Number of Clinical Complications | 2 years | Increased NTBI, serum iron, or transferrin saturation following transfusion is associated with increased risk of clinical adverse effects (i.e., new infections, SCD complications) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Transfusion Reactions | 2 years | Transfusion reactions are associated with RBC survival |
| Type I interferon (i.e., MxA protein assay) and other cytokines (i.e., IL-6, MCP-1, IFNgamma) | 2 years | Recipient inflammation pre-transfusion is associated with RBC survival |
| Rate of Alloimmunization | 2 years | Rate of new alloantibody formation |
| 4-hydroxynonenal [4-HNE] | 2 years | Recipient oxidative stress pre-transfusion is associated with RBC survival |
Countries
Brazil, United States
Outcome results
None listed