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): 18.0-999.0,  Sickle Cell Disease Age ≥18 by time of enrollment Diagnosis of SCD documented by genetic analysis (S/S, S/β-thalassemia-zero) Must not have medically eligible and available HLA-identical sibling donor or 10/10 allele-matched unrelated donor (within a year prior to harvest) (or refuses to have an allogeneic HSCT) Inadequate clinical response to hydroxyurea (HU), defined as any one of the following outcomes, while on HU for at least 3 months or more acute sickle pain crises requiring hospitalization no rise in Hb >1.5 gm/dl from pre-HU baseline or requires transfusion to maintain Hb > 6.0 gm/dL Has an episode of acute chest syndrome defined as development of a new pulmonary alveolar consolidation involving at least one complete lung segment associated with acute symptoms including: fever >38.5, chest pain, tachypnea, intercostal retractions, nasal flaring, use of accessory muscles of respiration, wheezing, rales, or cough not attributable to asthma or bronchiolitis) in the preceding two year period prior to enrollment. The acute chest syndrome event occurred despite adequate supportive care measures Or medical decision for other therapy (e.g. chronic transfusion program), or subject refusal to take HU The patient must be off HU for at least 30 days (+/ days) before PBSC collection  Patient has a medically eligible and available HLA-identical sibling donor or 10/10 allele-matched unrelated donor (unless they refuse to have an allogeneic HSCT) Cardiac evaluation: left ventricular ejection fraction (LVEF) < 40% or LV shortening fraction < 26% by cardiac echocardiogram or by MUGA scan or clinically significant ECG abnormalities Poorly controlled hypertension as determined by BP with systolic >135 or diastolic >95 mmHg despite treatment Pulmonary evaluation: baseline oxygen saturation of <85% or DLCO< 40% (corrected for Hb) Renal evaluation: serum creatinine >1.5x upper limit of normal for age or GFR<60 mL/min/1.73 m2 within 90 days prior to PBSC collection Hepatic evaluation: serum conjugated (direct) bilirubin > 2x upper limit of normal for age as per local laboratory or ALT and AST > 5 times upper limit of normal as per local laboratory within 90 days prior to PBSC collection Hematologic evaluation: Leukopenia (WBC< 3x103/uL) or neutropenia (ANC < 1.0x103/uL) or thrombocytopenia (platelet count < 100x103/uL) within 90 days prior to PBSC collection PT/INR or PTT >1.5x upper limit of normal or other clinically significant bleeding disorder to Liver Iron >10mg/g by T2* MRI (within 1 year prior to PBSC collection) Seropositivity for HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HTLV-1 (Human T-Lymphotropic Virus), or active Hepatitis B Virus, or active infection by CMV or parvovirus B19, based on positive blood PCR