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): 2.0-80.0,  Sickle Cell Disease Patients with any type of sickle cell disease who are at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, or C) or potentially modifiable complication(s) not ameliorated by hydroxyurea (D): A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct or hemorrhage on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR B. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s at baseline (without vaso-occlusive crisis) and/or pulmonary hypertension; OR C. Sickle hepatopathy defined as either ferritin >1000 mcg/L and platelet count < 250,000/uL (without vaso-occlusive crisis) OR direct bilirubin > 0.4 mg/dL and platelet count <250,000/uL (without vaso-occlusive crisis) D. Any one of the below complications Complication-Vaso-occlusive crises; Eligible for HSCT-Recurrent vaso-occlusive pain crises (at least 2 per year for the last 2 years) despite hydroxyurea Complication-Acute chest syndrome; Eligible for HSCT-any ACS while on hydroxyurea. Non-disease specific: A. Age greater than or equal to 18 years B. Haploidentical relative donor available C. Ability to comprehend and willing to sign an informed consent D. Negative serum beta-HCG E. Ejection fraction greater than or equal to 35% F. Glomerular filtration rate >60 mL/min/1.73m^2 by cystatin C-based or iothalamate-based or other equivalent GFR testing G. Adjusted DLCO greater than or equal to 35%  (any of the following would the subject from participating) 1. Available 6/6 HLA-matched sibling donor 2. ECOG performance status of 3 or more (See Appendix A) 3. Evidence of uncontrolled bacterial, viral, or fungal infections (currently taking medication and progression of clinical symptoms) within one month prior to starting the conditioning regimen. 4. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen. 5. Major anticipated illness or organ failure incompatible with survival from PBSC transplant 6. Pregnant or breast-feeding 7. Donor specific anti-HLA antibodies (DSAs) greater than or equal to 2000 Mean Fluorescence Intensity (MFI) 8. Patients seronegative for EBV who have EBV seropositive donors Haploidentical relative donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood for research. Related donors will be evaluated in accordance with existing Standard NIH Policies and Procedures for determination of and suitability for clinical donation. Note that participation in this study is offered to all related donors, but is not required for a do le that not all related donors will enroll onto this study -DONOR: None