Patient description: The patient is a 34-year-old African American man with the known history of Sickle cell disease comes to the clinic with severe bone pain. The patient had severe pain in his lower back that radiated to both thighs scored 9 out of 10. The patient has had positive history of sickle cell crises since childhood. He also had the same symptoms in past two weeks treated with oxycodone which was not beneficial to his pain. His PCP sent him to the emergency department to receive intra venous pain modulators. The patient is afebrile within the normal blood pressure. No splenomegaly was detected in the physical exam. He has no positive history of drug allergy. He won't smoke or uses any illicit drugs. The lab study is as bellow: Hgb: 8 g/dl WBC: 10000 /mm3 Plt: 300000 /ml MCV: 106 fL Hemoglobine electrophoresis: 91% HbS 6%HbF 3%HbA2 AST: 22 U/L ALT: 43 U/L Alk P: 53 U/L Ferritin: 1200 ng/ml

Clinical trial eligibility criteria: eligible ages (years): 16.0-40.0,  Sickle Cell Disease Diagnosis of severe sickle cell disease and have one or more of the following: 1. Clinically significant neurologic event (stroke) or any neurological deficit lasting > 24 hours 2. History of two or more episodes of acute chest syndrome (ACS) in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. asthma therapy and/or hydroxyurea). Acute Chest Syndrome (ACS) is defined as new pulmonary alveolar consolidation (or infiltrate) involving at least one complete lung segment associated with acute symptoms including one or more of the following: fever ≥ 38.5 Celsius, chest pain, tachypnea per age adjusted normal, intercostal retractions/nasal flaring/use of accessory muscles of respiration, wheezing, rales or cough that is not attributed to asthma or bronchiolitis. 3. History of three or more severe pain crises per year in the 2-year period preceding enrollment despite the institution of supportive care measures (i.e. a pain management plan and/or treatment with hydroxyurea). Pain Crisis is defined as new onset of pain that last for at least 2 hours for which there is no other explanation (i.e. vaso-occlusive, priapism). 4. Administration of regular red blood cell (RBC) transfusion therapy, defined as receiving 8 or more transfusions per year for greater than or equal to 1 year to prevent vaso-occlusive clinical complications (i.e. pain, stroke, and acute chest syndrome) 5. Trans-thoracic echocardiograph evidence of tricuspid valve regurgitant jet (TRJ) velocity greater than or equal to 2.7 m/sec Adequate physical function as measured by: 1. Karnofsky performance score greater than or equal to 60 2. Cardiac function: Left ventricular ejection fraction (LVEF) > 40%; or LV shortening fraction > 26% by cardiac echocardiogram or by multigated acquisition (MUGA) scan. 3. Pulmonary function: Pulse oximetry with a baseline O2 saturation of greater than or equal to 85% and diffusing capacity of the lungs for carbon monoxide (DLCO) > 40% (corrected for hemoglobin) 4. Renal function: Serum creatinine ≤ 1.5 x upper limit of normal for age and 24-hour urine creatinine clearance > 70 mL/min/1.73 m2 by radionuclide glomerular filtration rate (GFR); or GFR > 70 mL/min/1.73 m2 by radionuclide GFR. 5. Hepatic function: Serum conjugated (direct) bilirubin < 2x upper limit of normal for age as per local laboratory; and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 5 times upper limit of normal as per local laboratory. Patients whose hyperbilirubinemia is the result of hyperhemolysis, or a severe drop in hemoglobin post blood transfusion, are not excluded 6. If the patient has been receiving chronic transfusion therapy for greater than or equal to 1 year and has clinical evidence of iron overload by serum ferritin (mean of 3 ferritin levels >1000 and chronic transfusions >20 in a lifetime or MRI), evaluation by liver biopsy is required. Histological examination of the liver must document the absence of cirrhosis, bridging fibrosis and active hepatitis. The absence of bridging fibrosis will be determined using the histological grading and staging scale as described by Ishak and colleagues (1995) Patients must have a related or unrelated bone marrow donor with HLA-matched at 8 of 8 HLA-A, B, C, and DRB1 loci by allelic testing. Umbilical cord blood or peripheral blood stem cell donors will not be accepted  Patients with cirrhosis of the liver, uncontrolled bacterial, viral or fungal infection in the 6 weeks before enrollment, or seropositivity for HIV Patients who have received prior HCT Patients who within 3 months of enrollment have participated in another clinical trial in which the patient received an investigational drug or device or off-label use of a drug or device Patients who demonstrate lack of compliance with prior medical care Patients who are unwilling to use approved contraception for at least 6 months after transplant Patients who have a history of substance abuse in the last 5 years that interferes with their care Patients who are pregnant or breast feeding Patients unable to provide consent