A Reduced Toxicity Allogeneic Unrelated Donor Stem Cell Transplantation (SCT) for Severe Sickle Cell Disease

Inclusion Criteria: Patients must have sickle cell disease (genotype Hb SS or Sß° thalassemia), AND must have 1 or more of the following clinical complications related to Sickle cell disease: 1. A clinically significant neurologic event (stroke) or any neurologic defect lasting \>24 hours, that is accompanied by an infarct on cerebral MRI. 2. Minimum of two episodes of acute chest syndrome (defined as new pulmonary alveolar consolidation involving at least 1 complete lung segment associated with acute symptoms including fever, chest pain, tachypnea, wheezing or cough) despite adequate supportive care measures (example: asthma therapy, hydroxyurea). 3. History of severe pain episodes defined as 3 or more severe pain events per year in the 2 years prior to enrollment despite adequate supportive care measures and hydroxyurea trial (i.e. Hydroxyurea non-responders). Pain may occur in typical sites associated with vaso-occlusive painful events and cannot be explained by causes other than vaso-occlusion mediated by sickle cell disease. 4. Recurrent priapism. 5. Osteo-necrosis of multiple joints 6. Evidence of Pulmonary Hypertension as evidenced by Tricuspid Regurgitation jet velocity (TRV) \> 2.5 m/s on Echocardiogram. 7. Red cell allo-immunization (≥ 2 antibodies) during long term transfusion therapy. Exclusion Criteria: 1. Invasive bacterial, viral or fungal infections within 1 month prior to starting conditioning therapy. 2. Female patients who are Pregnant (Beta HCG +) or breastfeeding. 3. HIV positive patients. 4. Patients with HLA-matched related family donors are not eligible for this study. 5. Prior myeloablative allogeneic HCT. 6. Patients on chronic transfusion therapy for ≥ 1 year with evidence of cirrhosis of liver on biopsy 7. Any significant concurrent disease, illness, severe cognitive delay or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.