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): 4.0-80.0,  Sickle Cell Disease Thalassemia Stem Cell Transplantation Graft vs Host Disease recipients (must fulfill one disease category in 1.0 and all of 2.0) 1.0 Disease specific 1.1 Patients with sickle cell disease (Hb SS, SC, or S beta-thal) at high risk for disease-related morbidity or mortality, defined by having severe end-organ damage (A, B, C, D, or E) or potentially modifiable complication(s) not ameliorated by hydroxyurea (F) A. Stroke defined as a clinically significant neurologic event that is accompanied by an infarct on cerebral MRI or cerebral arteriopathy requiring chronic transfusion therapy; OR B. Sickle cell-related renal insufficiency defined by a creatinine level greater than or equal to 1.5 times the upper limit of normal and kidney biopsy consistent with sickle cell nephropathy OR nephrotic syndrome OR creatinine clearance less than < 50mL/min OR requiring peritoneal or hemodialysis; OR C. Tricuspid regurgitant jet velocity (TRV) of greater than or equal to 2.5 m/s 40, 41 at baseline; OR D. Recurrent priapism defined as at least 2 episodes of an erection lasting >4 hours involving the corpora cavernosa and corpus spongiosa; OR E. Sickle hepatopathy defined as ferritin >1000mcg/L OR direct bilirubin >0.4 mg/dL at baseline F. Any one of the below complications Complication/ Eligible for hydroxyurea*/ Eligible for HSCT Vaso-occlusive crises/ At least 3 hospital admissions in the last year/ More than one hospital admission in the last year while on maximal tolerated dose of hydroxyurea (at MTD for at least 6 months) Acute chest syndrome/ 2 prior ACS/ any ACS while on hydroxyurea (at MTD for at least 6 months)  recipient (any of the following would the subject from participating) 1. ECOG performance status of 3 or more 2. 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. Patients with fever or suspected minor infection should await resolution of symptoms before starting the conditioning regimen. 3. Major anticipated illness or organ failure incompatible with survival from PBSC transplant 4. Pregnant or lactating 5. We will measure anti-A, anti-B, and/or other red cell antibody titers from the first cohort to determine the feasibility of transplanting patients with pre-existing antibodies (major ABO mismatch or other anti-donor red cell antibody). The information gathered from this cohort of patients will help to determine if the titer or antibody to a specific antigen needs to be incorporated in the adult donor 1. 6/6 HLA matched family donor 2. Fit to receive filgrastim (G-CSF) and to give peripheral blood stem cells (blood counts and blood pressure within DTM standards no history of congestive heart failure or unstable angina, and no history of stroke) 3. Ability to comprehend and willing to sign an informed consent; assent obtained from minors adult donor: (any of the following would the donor from participating) 1. Pregnant or breastfeeding 2. HIV positive 3. Hemoglobin S greater than or equal to 50%, or B-thalassemia intermedia pediatric donor Pediatric donors will undergo apheresis as a Standard of Care procedure under NHLBI protocol 94-H-0010. These donors must meet the NIH Department of Transfusion Medicine (DTM) requirements for apheresis donation. pdiatric donors will be enrolled onto this study in order to provide a research blood sample. These donors must have met standard requirements for apheresis donation first