Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies

1. Inclusion Criteria The following criteria are established to identify subjects with hemoglobinopathies, hematologic or bone marrow failure syndromes who have a high predicted morbidity and are at risk for early mortality: * Patients with alpha or beta thalassemia major. * Patients with Diamond-Blackfan anemia and other bone marrow failure syndromes, characterized by severe chronic anemia. * Patients with other complex and transfusion-dependent hemoglobinopathies, including sickle cell disease. * Patients with sickle disease who have one or more of the following: * Overt or silent stroke * Neurocognitive impairment * Pain crises 2 or more episodes per year for past year * One or more episodes of acute chest syndrome * Osteonecrosis involving 1 or more joints * Evidence of retinopathy * Priapism * Microalbuminuria or evidence of sickle cell nephropathy * Alloimmunization Subjects must also meet all of the following general inclusion criteria: * Subjects must have a related donor which can consist of Histocompatibility Leukocyte Antigen (HLA)-matched donor up to haploidentical match, mismatched for 1, 2 or 3 HLA-A, B or -DR loci. * Subjects must have adequate cardiopulmonary function as documented by echocardiogram or radionuclide scan. (Shortening fraction \>26% or ejection fraction \>40% or ≥ 80% of normal value for age). * Subjects must have adequate pulmonary function documented by Forced expirator…