T-Cell Depleted Alternative Donor Bone Marrow Transplant for Sickle Cell Disease (SCD) and Other Anemias

Inclusion Criteria 1. 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. * Hepatic transaminases (ALT/AST) ≤ 3 x upper limit of normal. * Liver MR imaging for iron content should be performed in all patients with Ferritin \> 500 ng/mL. If hepatic iron content \> 10mg Fe/g liver should have hepatology consultation and liver biopsy to confirm absence of cirrhosis, fibrosis or hepatitis. * Adequate cardiac function as measure by echocardiogram (shortening fraction \> 26% or ejection fraction \> 40% or \>80% of age-specific normal). * Pulmonary evaluation testing demonstrating FEV1/FVC ≥ 60% of predicted for age and/or resting pulse oximeter ≥ 92% on room air. * Cardiology clearance to proceed with conditioning regimen and HSCT. * Pulmonology clearance to proceed with conditioning regimen and HSCT. 6. Subjects must be human immunodeficiency virus (HIV) negative by PCR. 7. Negative pregnancy test for females ≥10 years old or who have reached menarche, unless surgically sterilized. 8. All females of childbearing potential and sexually active males must agree to use an FDA approved method of birth control for up to 24 months after BMT or for as long as they are taking any medication that may harm a pregnancy, an unborn child or may cause a birth defect. 9. Subject and/or parent guardian will also be counseled regarding the potential risks of infertility following BMT and advised to discuss sperm banking or oocyte harvesting (Refer to section, 10. Hydroxyurea must have been trialed and failed in patients with sickle cell disease. Patient Exclusion Criteria 1. 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.