Conditions: Sickle Cell Disease Thalassemia Severe Congenital Neutropenia Diamond-Blackfan Anemia Shwachman-Diamond Syndrome
Keywords: high risk hemoglobinopathy stem cell transplant donor lymphocyte infusion transfusion dependent stem cell donor cord blood marrow transfusion dependent non-malignant hematologic disorders
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 22
Healthy volunteers: no

Brief summary:
This study tests the clinical outcomes of one of two preparative regimens (determined by available donor source) in patients with non-malignant hemoglobinopathies. The researchers hypothesize that these regimens will have a positive effect on post transplant engraftment and the incidence of graft-versus-host-disease.

Regimen A2 has replaced Regimen A in this study. Two patients were treated on Regimen A but did not have evidence of initial engraftment thus triggering the stopping rule for that arm of this study.

Detailed description:
Prior to transplantation, subjects will receive either:

Cyclophosphamide, Fludarabine, Campath, Total body irradiation (TBI)

Or

Busulfan, Cyclophosphamide, antithymocyte globulin (ATG), granulocyte colony-stimulating factor (GSCF)

These drugs (and the radiation) are being given to help the new stem cells take and grow. On the day of transplantation, subjects will receive stem cells transfused via intravenous (IV) catheter.

After stem cell transplantation, subjects will be given cyclosporine-A and mycophenolate (MMF)/or Methylprednisone/or Methotrexate to reduce the risk of graft-versus-host disease, the complication that occurs when the donor's stem cells react against the patient.

Arms:
arm 1: Full Preparative Regimen for subjects with matched donors using Busulfan on Day -8 and -7, Fludarabine on Day -6 through -2, antithymocyte globulin (ATG) on Day -2 through -1, total lymphoid radiation (TLI) on Day -1, stem cell infusion on Day 0. arm 2: Myeloablative Preparative Regimen for subjects with HLA identical sibling donors consists of Busulfan on day -9 through -6, Cyclophosphamide on day -5 through -2, ATG on day -3 through -1, stem cell infusion on Day 0 and Granulocyte Colony Stimulating Factor on day -3 until ANC \>2500 x 2 days. arm 3: Patients with sickle cell disease or thalassemia who do not have an HLA-identical sibling donor or who has pre-existing organ dysfunction making myeloablative condition ineligible will receive Campath on day -10 through -6, Cyclophosphamide on day -7, Fludarabine on day -6 through -2, total body irradiation (TBI) on day -1, stem cell infusion on Day 0.

Interventions: intervention 1: Busulfan, Fludarabine, ATG, TLI intervention 2: Busulfan, Cyclophosphamide, ATG, GCSF intervention 3: Campath, Fludarabine, Cyclophosphamide intervention 4: Total Body Irradiation intervention 5: Stem cell infusion
Intervention descriptions: intervention 1: Busulfan 0.8 mg/kg/dose intravenous (IV) Days -8 and -7 Fludarabine 35 mg/m2 IV Days -6 through -2 Antithymocyte globulin (ATG) 30 mg/kg IV Days -2 and -1 Total lymphoid radiation 300 cGy intervention 2: Busulfan 0.8 mg/kg/dose intravenous (IV) Days -9 through -6 Cyclophosphamide 50 mg/kg IV Days -5 through -2 ATG 30 mg/kg IV Day -1 GCSF 5 mcg/kg/day IV until ANC \>2500 x 2 days. intervention 3: Receives Campath-1H 0.2 mg/kg Days -10 through -6, Fludarabine 35 mg/m2 intravenous (IV) Days -6 through -2, total body irradiation (TBI) 300 cGy Day -1. intervention 4: 300 cGY Day -1 intervention 5: Given Day 0

Protocol document: