Stem Cell Transplant for Bone Marrow Failure Syndromes

Brief Title

Stem Cell Transplant for Bone Marrow Failure Syndromes

Official Title

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

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

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.

Study Phase

Phase 2/Phase 3

Study Type


Primary Outcome

Number of Patients Alive (Survival) at 2 Years

Secondary Outcome

 Number of Patients Alive at Three Years (Survival)


Diamond-Blackfan Anemia


Stem cell transplant

Study Arms / Comparison Groups

 Bone Marrow Failure Disorders
Description:  Patients with Diamond-Blackfan Anemia, Kostmann's Neutropenia, Shwachman-Diamond Syndrome


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

June 2000

Completion Date

March 2009

Primary Completion Date

March 2009

Eligibility Criteria

        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

               -  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




N/A - 35 Years

Accepts Healthy Volunteers



Paul Orchard, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Masonic Cancer Center, University of Minnesota

Study Sponsor

Paul Orchard, MD, Principal Investigator, University of Minnesota Medical Center

Verification Date

December 2017