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Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism

Phase 2/Phase 3
50 Years
Open (Enrolling)
Sickle Cell Disease, Thalassemia, Severe Congenital Neutropenia, Diamond-Blackfan Anemia, Shwachman-Diamond Syndrome

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Trial Information

Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism

Prior to transplantation, subjects will receive either:

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


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)

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.

Inclusion Criteria:

- Patients with Sickle Cell Disease/Thalassemia (SCD/THAL) 0-50 years of age with an
acceptable stem cell donor and disease characteristic defined by the following:

- Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting
longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or
cerebral arteriogram or MRI angiographic study and impaired neuropsychological

- Acute chest syndrome with a history of recurrent hospitalizations or exchange

- Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more
years or recurrent priapism,

- Impaired neuropsychological function and abnormal cerebral MRI scan

- Stage I or II sickle lung disease,

- Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration
rate [GFR] 30-50% of the predicted normal value)

- Bilateral proliferative retinopathy and major visual impairment in at least one

- Osteonecrosis of multiple joints with documented destructive changes

- Requirement for chronic transfusions but with red blood cell (RBC)
alloimmunization >2 antibodies during long term transfusion therapy

- Patients with transfusion dependent alpha- or beta-thalassemia 0-35 years of age with
an acceptable stem cell donor as defined in the criteria in section above.

- Patients with other non-malignant hematologic disorders that are
transfusion-dependent or involve other potentially life-threatening cytopenias
(including but not limited to Severe Congenital Neutropenia, Diamond-Blackfan Anemia
and Shwachman-Diamond Syndrome) who are 0-35 years of age with an acceptable stem
cell donor

- Second Transplants

- Patients with sickle cell disease or thalassemia who have failed to engraft or
have autologous recovery after a myeloablative SCT regimen or non-myeloablative
regimen are eligible for this protocol.

- Regimen A2 will be utilized for patients with sickle cell disease or thalassemia
who do not have an HLA-identical sibling donor or for any patient who has
pre-existing organ dysfunction making them ineligible for a myeloablative
preparative regimen.

- Regimen B will be utilized for patients with sickle cell disease or thalassemia
who have an HLA-identical sibling donor.

- Patients must meet above criteria.

- If the patient has received prior radiation therapy, eligibility to receive
additional radiation therapy must be determined by Dr. Dusenbery

- If first transplant was a non-myeloablative regimen, the second transplant can
occur at any time

- If the first transplant was a myeloablative regimen, then the second transplant
must be > 6 months from the first transplant

Exclusion Criteria:

- Patients with one or more of the following:

- Karnofsky or Lansky performance score <70

- Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on

- Stage III-IV lung disease

- GFR<30% predicted

- Pregnant or lactating females

- Active serious infection whereby patient has been on intravenous antibiotics for one
week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity

- Psychologically incapable of undergoing bone marrow transplant (BMT) with associated
strict isolation or documented history of medical non-compliance

- Patients not able to receive total lymphocytic irradiation (TLI) due to prior
radiation therapy

Type of Study:


Study Design:

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

Outcome Measure:

Grade 3-4 Regimen Related Toxicity

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Angela Smith, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Institutional Review Board

Study ID:




Start Date:

June 2002

Completion Date:

June 2016

Related Keywords:

  • Sickle Cell Disease
  • Thalassemia
  • Severe Congenital Neutropenia
  • Diamond-Blackfan Anemia
  • Shwachman-Diamond Syndrome
  • high risk hemoglobinopathy
  • stem cell transplant
  • donor lymphocyte infusion
  • transfusion dependent
  • stem cell donor
  • cord blood
  • marrow
  • transfusion dependent non-malignant hematologic disorders
  • Anemia
  • Anemia, Sickle Cell
  • Hemoglobinopathies
  • Neutropenia
  • Thalassemia
  • Bone Marrow Diseases
  • Lipomatosis
  • Exocrine Pancreatic Insufficiency
  • Anemia, Diamond-Blackfan



Masonic Cancer Center, University of Minnesota Minneapolis, Minnesota  55455