Clinical Importance of Treating Iron Overload in Sickle Cell Disease

Inclusion Criteria: * Male or female patients with sickle cell anemia (SS or SB thalassemia) with transfusional iron overload. * Currently not on chronic or frequent transfusion * Age equal or greater then 14 years * Patients with iron overload from repeated blood transfusion, as defined by one of the following: 1. For patients greater then 16 years old receiving simple transfusions: estimated lifetime history of receipt of at least 100 ml/kg or 15 adult units of packed red blood cells, OR 2. For patients equal to or less then 16 years old receiving simple transfusions: estimated lifetime history of receipt of at least 100 ml/kg of packed red blood cells, OR 3. For any patient: liver iron content equal/greater then 3 mg Fe/g dw as measured by biopsy or magnetic resonance imaging who have not been adequately chelated since that measurement, OR 4. a serum ferritin equal/greater then 1000 ng/mL on at least two occasions, at least two weeks apart, during the prior year. Samples must be obtained in the absence of concomitant infection * Life expectancy equal/greater then 12 months * Sexually active women must use an effective method of contraception, or must have undergone clinically documented total hysterectomy and/or oophorectomy, or tubal ligation or be postmenopausal (defined as amenorrhea for at least 12 months) Inclusion criteria for treatment pilot study * Meets all inclusion criteria for screening * LIC by MRI greater than or equal to 8 mg/g. Exclusion Criteria: * Blood transfusion within 12 weeks of the day 0 hemolysis labs * Currently requires blood transfusion more than three times a year. * Contraindication to MRI, including cardiac pacemaker, brain aneurysm clip, implanted neurostimulator, insulin pump, cochlear implant, metal slivers in the eyes, intrauterine device or any other MRI incompatible metal implants or intractable claustrophobia. * Serum creatinine above the upper limit of normal * Concomitant treatment with erythropoietin or its analogs. * AST or ALT greater then 250 U/L during screening (patients may be re-screened at a later date if the cause of the elevation is known to be due to a transient process). * Patients receiving currently on chelation will be asked to stop for one week before starting or restarting Exjade. (a equal/greater then 1 week washout period prior to first dose of study drug is required) * History of HIV positive test result (ELISA or Western blot) * History of drug or alcohol abuse within the 12 months prior to enrollment * Patients with uncontrolled systemic hypertension * Severe cardiac insufficiency (NYHA III or IV), with uncontrolled and/or unstable cardiac or coronary artery disease not controlled by standard medical therapy * Patients with a diagnosis of or history of clinically relevant ocular toxicity related to iron chelation * Systemic diseases (cardiovascular, renal, hepatic, etc.) which would prevent study treatment * Pregnancy (as documented in required screening laboratory test) or breast feeding * Patients who received treatment with systemic investigational drug within the past 4 weeks or topical investigational drug within the past 7 days or are planning to receive other investigational drugs while participating in the study * Other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of study drug * History of non-compliance to medical regimens or patients who are considered potentially unreliable and/or not cooperative