Conditions: Diamond-Blackfan Anemia Kostmann's Neutropenia Shwachman-Diamond Syndrome
Keywords: Stem cell transplant T-cell depletion TLI bone marrow failure disorders
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 10
Healthy volunteers: no

Brief summary:
The researchers hypothesize that it will be possible to perform unrelated bone marrow or cord blood transplants in a safer manner by using less intensive therapy yet still achieve an acceptable level of donor cell engraftment for non-malignant congenital bone marrow failure disorders.

Detailed description:
Prior to transplantation, subjects will receive the drugs busulfan (orally or through the catheter), as well as fludarabine and anti-thymocyte globulin (ATG) via the catheter. Busulfan, fludarabine and ATG will be given with Total Lymphoid Irradiation (TLI) to help the new donor bone marrow take and grow after transplantation.

Those patients receiving donor marrow will have the T cells (a type of white blood cell in the donor marrow) removed to lower the risk that the new marrow will react to their body, a condition called Graft-Versus-Host-Disease (GVHD). After bone marrow transplantation, subjects will receive drugs to help prevent GVHD, including cyclosporin and mycophenolate mofetil (MMF).

Blood samples are taken at day 28, day 60, day 100, 1 year and as required by medical status yearly for five years after transplant to evaluate how well the new marrow is growing. A bone marrow biopsy is required at day 21, at day 100 and 1 year.

Arms:
arm 1: Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome

Interventions: intervention 1: Stem cell transplant intervention 2: Fludarabine monophosphate intervention 3: Total lymphoid irradiation intervention 4: Busulfan intervention 5: anti-thymocyte globulin
Intervention descriptions: intervention 1: Stem cell transplant on Day 0 - healthy marrow from an unrelated individual. A minimum of 1.0 x 10\^9/kg nucleated cells/kg ideal body weight will be collected with a goal of 2.0 x 10\^9/kg. intervention 2: fludarabine 175 mg/m\^2 (total) on Days -6 through -3. intervention 3: Dose 500 cGy radiation therapy to specific areas of the body intervention 4: Busulfan 8 mg/kg (total) on Days - 8 and -7 (orally or through the catheter), intervention 5: anti-thymocyte globulin (ATG) 15 mg/kg on days -2 and -1 via catheter

Protocol document: