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): 18.0-45.0,  Sickle Cell Anemia Sickle Cell-hemoglobin C Disease Sickle Cell-β0-thalassemia Patient Selection: i) Patients with sickle cell disease (sickle cell anemia, sickle cell-hemoglobin C disease, or sickle cell-β0-thalassemia) confirmed by hemoglobin electrophoresis. ii) Patients should have one or more of the following: 1. History of acute chest syndrome requiring recurrent hospitalization or exchange transfusion (Acute chest syndrome is defined as pulmonary infiltrate involving at least one complete lung segment, consistent with alveolar consolidation but not atelectasis, accompanied by chest pain, fever, cough, tachypnea or wheezing) 2. History of nonhemorrhagic stroke or central nervous system event lasting longer than 24 hours 3. Recurrent vaso-occlusive pain (≥5 episodes during the past two years) or recurrent priapism requiring hospitalization or visits to the emergency room or sickle cell day unit 4. Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration rate 30-50% of normal predicted value) with progression on ACE inhibitor therapy iii) Patient must have failed therapy with hydroxyurea, as HU as evidenced by at least 6 months of maximum HU dosage for sickle cell disease, i.e. dose escalation to a level which caused some minimal hematologic toxicity in terms of CBC values. Failure to respond must also be documented by no significant increase in subjects HbF levels at this maximally tolerated dosage.AND development/ persistence of items listed in (ii) Patients who are deemed not eligible for hydroxyurea by the primary hematologist will be considered eligible without having failed hydroxyurea. Non-eligibility for hydroxyurea therapy is based on: (1) the diagnoses of SC disease and sickle cell-β0-thalassemia in which no clear evidence supports the use of hydroxyurea therapy and thus treatment with hydroxyurea is not considered the standard of care in these entities (2) the presence of high hemoglobin F levels in patients with sickle cell anemia and documented Hereditary Persistence of Fetal Hemoglobin (HPFH) in which hydroxyurea is not considered the standard of care (3) severe adverse reactions to hydroxyurea in patients with sickle cell anemia based on, but not limited to, count suppression, GI intolerance, and dermatomyositis Patient unwillingness to be compliant with hydroxyurea therapy is not an acceptable reason for non-eligibility iv) Patients must have an acceptable related donor 1. who is matched at the HLA-A;B; C; DR loci (8 of 8 match) or mismatched for at most one locus (7 of 8 match) (well matched related donor 2. who is mismatched at 2-4 alleles (haplo-identical) v) Patient age greater than 18 years vi) ECOG performance status 0-2/ Karnofsky 70-100% vii) Written informed consent obtained from the patient. viii) Transaminases <3X ULN; patients with transaminases greater than the ULN but less than 3XULN will be evaluated by the hepatology service and will undergo further imaging and biopsy as deemed necessary by hepatology. They will not be considered eligible unless cleared by hepatology  Patient Selection: i) Pregnancy/ unwillingness to use adequate contraception during study period ii) Liver disease including 1. Acute hepatitis (transaminases >3x normal value) 2. Chronic hepatitis C 3. Chronic hepatitis B or history of exposure to hepatitis B iii) Cardiac ejection fraction < 50% iv) Pulmonary hypertension as evidenced by findings on resting echocardiogram of pulmonary artery systolic pressure ≥ 40 mmHg or any evidence of right ventricular dysfunction (hypokinesis or RV dilation) v) Severe renal impairment (GFR <30% of predicted normal value) vi) Severe residual functional neurologic impairment (other than hemiplegia alone) vii) DLCO ≤50 viii) Any evidence of infection by the human immunodeficiency virus ix) Psychiatric disorder that would preclude patients from signing an informed consent x) Severe neuro-cognitive or executive function making informed consent possible