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Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

Phase 2/Phase 3
35 Years
Not Enrolling
Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome

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Trial Information

Bone Marrow Transplantation for Non-Malignant Congenital Bone Marrow Failure Disorders

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.

Inclusion Criteria:

- Patients eligible for transplantation under this protocol will be <35 years of age,
and will be diagnosed with:

- a bone marrow failure syndrome unresponsive to available therapy, including but
not limited to Diamond-Blackfan anemia, Shwachman Diamond syndrome or Kostmann's
neutropenia but exclusive of aplastic anemia.

- Diamond Blackfan Anemia:

- Patients must show evidence of steroid resistance requiring equivalent of >6
transfusions yearly despite steroid therapy.

- Evidence of developing aplasia or myelodysplasia will also be criteria for

- Kostmann's Neutropenia, Shwachman-Diamond syndrome:

- Patients must have been previously diagnosed as having a clinical picture
characteristic of Shwachman-Diamond syndrome (exocrine pancreatic insufficiency,
growth retardation, metaphyseal dysostosis, neutropenia), or must have a bone
marrow aspirate consistent with Kostmann's neutropenia, with no evidence of
acute leukemia.

- Patients must have failed therapy with granulocyte-colony stimulating factor
(G-CSF), as determined by an inability to maintain an absolute neutrophil count
(ANC) >750 cells/ml(3), or manifesting recurrent infections despite G-CSF
administration resulting in life threatening infections or repeated
hospitalizations (<4 /year).

Exclusion Criteria:

- Patients >35 years of age

- Karnofsky score <70%

- Hepatic dysfunction as determined by bilirubin >3.0, ALT >150, or active hepatitis

- Pulmonary function tests with forced volume vital capacity (FVC) and forced
expiratory volume (FEV) <70%; O2 saturation <94%

- Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.

- Cardiac compromise, with left ejection fraction <45%.

- Severe, stable neurologic impairment.

- Human immunodeficiency virus (HIV) positivity.

- Pregnant or lactating females

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Patients Alive (Survival) at 2 Years

Outcome Description:

Calculated from day 1 of transplant to last contact.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Paul Orchard, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Minnesota Medical Center


United States: Institutional Review Board

Study ID:




Start Date:

June 2000

Completion Date:

March 2009

Related Keywords:

  • Diamond-Blackfan Anemia
  • Kostmann's Neutropenia
  • Shwachman-Diamond Syndrome
  • Stem cell transplant
  • T-cell depletion
  • TLI
  • bone marrow failure disorders
  • Anemia
  • Neutropenia
  • Pancytopenia
  • Bone Marrow Diseases
  • Lipomatosis
  • Exocrine Pancreatic Insufficiency
  • Anemia, Diamond-Blackfan



University of Minnesota Medical CenterMinneapolis, Minnesota  55455