TCR Alpha Beta T-cell Depleted Haploidentical HCT in the Treatment of Non-Malignant Hematological Disorders in Children

Eligibility Criteria

• 1. Severe sickle cell disease (HbSS, HbSC, HbSB0, HbSB+, HbSD, HbSE) with at least one of the following criteria:
• 1. Cerebrovascular accident lasting longer than 24 hours
• 2. Impaired neuropsychological function with abnormal brain MRI/MRA
• 3. Patients with frequent (≥ 3 per year for preceding 2 years) painful vaso-occlusive episodes
• 4. Recurrent (≥ 3 in lifetime) acute chest syndrome events which have necessitated erythrocyte transfusion therapy
• 5. Any combination of ≥ 3 acute chest syndrome episodes and vaso-occlusive pain episodes yearly for 3 years and have failed treatment with hydroxyurea (HU) (at least 6 months on maximum tolerated dose) or who are intolerant to HU therapy
• 2. Thalassemia major with at least one of the following criteria:
• 1. Transfusion dependency defined as receiving 8 or more transfusions per year
• 2. Thalassemia diagnosis documented by clinical assessment, laboratory evidence with microcytic anemia and absence of HbA (\< 10%) on electrophoresis and or confirmation by DNA analysis of alpha and beta gene loci
• 3. Genotypically proven thalassemia major for children \< 2 years of age even in the absence of transfusion dependency
• 4. Lucarelli class 1 or 2 risk status (i.e. with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor response to chelation therapy)
• 3. Bone marrow failure syndromes and autoimmune cytopenias:
• 1. Severe Aplastic Anemia refractory to immunosuppressive therapy
• 2. Diamond Blackfan Anemia refractory to conventional therapy
• 3. Inherited Bone Marrow Failure Syndromes such as Fanconi anemia and Shwachman-Diamond syndrome with progressive marrow failure (without cytogenetic evidence of MDS/AML)
• 4. Severe Congenital Neutropenia
• 5. Congenital Amegakaryocytic Thrombocytopenia
• 6. Glanzmann Thrombasthenia
• 7. Autoimmune Cytopenias refractory to conventional treatment (including Pure red cell aplasia, Evan's syndrome, Immune thrombocytopenia, autoimmune hemolytic anemia)
• 8. Other marrow failure disorders not otherwise specified
• 1. Participants who have an HLA-matched sibling who is able and willing to donate bone marrow. Patients with a HLA-matched unrelated donors are not excluded.
• 2. Pregnant or breastfeeding females.
• 3. Patient has HIV or uncontrolled fungal, bacterial or viral infections.
• 4. Patient has received prior solid organ transplant.
• 5. Patient has active GVHD (\> grade II) or chronic extensive GVHD due to a previous allograft at the time of inclusion.
• 6. For patients with hemoglobinopathy, liver biopsy is necessary if the patient has received chronic transfusions for over a year and has two ferritin levels of ≥ 1000 ng/ml. Patients with cirrhosis, extensive bridging hepatic fibrosis, or active hepatitis are excluded from enrollment.