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): 5.0-40.0,  Sickle Cell Anemia Beta-thalassemia Major Diamond-blackfan Anemia Patient, parent, or legal guardian must have given written informed consent and/or assent according to FDA guidelines. 2. Ages 5 years to 40 years, at time of consent. 3. Diagnosis of Sickle Cell Disease (Hemoglobin SS, Sβ0-thalassemia) complicated by any of the following Recurrent acute painful episodes (also known as vaso-occlusive crises; VOC) despite supportive care, minimum of 2 new pain events per year requiring hospitalization for parenteral pain management in the previous 2 years Recurrent acute chest syndrome (ACS) despite supportive care, minimum of 2 episodes in preceding 2-year period Stroke or neurologic event lasting > 24 hours with an accompanying infarct on MRI in any patient for all ages; Brain MRI with silent infarct without clinical event in patients ≤ 16 years Chronic transfusion therapy defined as > 8 packed red blood cell transfusions per year in the year prior to enrollment and/or evidence of red blood cell alloimmunization Elevated transcranial Doppler velocities > 200 cm/s, via the non-imaging technique or > 185 cm/s by the imaging technique measured on 2 separate occasions ≥ 1-month apart Elevated TRV > 2.6m/s in patients ≥ 16 years old Sickle-related renal insufficiency and/or sickle hepatopathy and/or any irreversible end-organ damage in patients ≥ 16 years old. OR Diagnosis of beta-thalassemia or Diamond-Blackfan anemia complicated by transfusion dependence with evidence of iron overload. 4. A minimum donor match of 4/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci in the related setting or minimum donor match of 6/8 via high resolution HLA typing at HLA-A, -B, -C, -DRB1 loci (with the DRB1 locus as a full match requirement). An unrelated donor and cord blood search must have been completed without an eligible 8/8 matched unrelated donor or 6/8 cord blood unit available. Patients who may have acceptable cord blood donor options (4/6 or better) but are limited by cell dose of a single cord will also be eligible for the proposed study. 5. Adequate function of other organ systems as measured by Creatinine clearance or GFR ≥ 45 ml/min/1.73m  Patients with alternate, superior donor options (matched sibling donor or matched unrelated donor). 2. Patients who have undergone stem cell transplantation in the 6 months prior to anticipated conditioning. 3. Patients with history of a central nervous system (CNS) event within six months prior to start of conditioning (patient will be delayed until eligible). 4. Patients who are pregnant or lactating 5. Patients with uncontrolled bacterial, viral or fungal infection 6. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study