Multi-Center Study of Iron Overload: Pilot Study

UCSF Benioff Children's Hospital Oakland20 enrolled

Overview

The purpose of this study is to initiate pilot studies to demonstrate that a sufficient number of iron-overloaded thalassemia, SCD and DBA populations with similar duration of chronic transfusion, and age at start of transfusions would be available for a confirmatory study and to validate that proposed multicenter MRI and biochemical studies can be completed. The study will examine the hypothesis that a chronic inflammatory state in Sickle Cell Disease (SCD) leads to hepcidin- and cytokine-mediated iron withholding within the RES (reticuloendothelial system), lower plasma NTBI (non transferrin bound iron) levels, less distribution of iron to the heart in SCD.

A detailed iron burden, transfusion and chelation history will be obtained from chart review or from participant recall. Iron burden data will include: 1) documentation of liver iron, and 2) average annual ferritin values. Transfusion data will include: (1) age at onset of regular transfusions, (2) years of chronic transfusion therapy, and (3) pre-transfusion Hb calculated as average of all assessments for each year. MRI will be performed measuring pituitary, cardiac, and liver iron. Laboratory samples should be obtained pre-transfusion and mid-cycle. All interviews, exams, laboratory tests, study procedures and MRI assessments should be completed within a 0 to 12 weeks time span. In addition, a healthy control group will also be recruited with similar age, gender, and ethnicity as the disease groups.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Sickle Cell Disease Thalassemia Diamond-Blackfan Anemia

Eligibility

Sex: ALLMin age: 16 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 10-20 years of transfusion (defined as 0.2-0.6mg Fe/kg/day exposure with annual ferritin levels greater than 2500 in at least 60% of years of chronic transfusion); * 0 to 9 years old at the initiation of chronic transfusions; no exchange transfusions in the previous 6 months * iron overload documented by either liver biopsy, MRI or SQUID with estimated LIC of greater than 7 mg/g dry wt in the previous 6 months or ferritin level greater than 1500mg/dl. Exclusion Criteria: * Patients with HbSC, HbS/β thalassemia * Pacemaker (active or inactive) or other implanted magnetic devices, severe claustrophobia, or other contraindications to MRI; Unable to remove ferro-magnetic objects from the body in regions to be imaged (e.g., jewelry or piercing) * Presence of any other condition which, in the opinion of the investigator, would make the patient unsuitable for enrollment; * Any chronic inflammatory illness other than the SCD, TM or DBA; * Any acute illness within a 14 day period prior to blood sampling; * Patients receiving intensive chelation in the 6 months prior to enrollment including deferoxamine 24 hours per day, 7 days per week or combination treatment with 2 chelators * Pregnancy

Outcomes

Primary Outcomes

Pilot study of biochemical mechanisms of iron deposition in patients with Sickle Cell Disease, Thalassemia and Diamond-Blackfan Anemia.

To examine the hypothesis that a chronic inflammatory state in Sickle Cell Disease (SCD) leads to hepcidin- and cytokine-mediated iron withholding within the RES (reticuloendothelial system), lower plasma NTBI (non transferrin bound iron) levels, less distribution of iron to the heart in SCD, and finally lower uptake and enhanced export of NTBI by cardiomyocytes conditioned by SCD serum, when compared with similarly iron overloaded patients with beta thalassemia and diamond blackfan anemia.