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Allogeneic Stem Cell Transplantation Following Nonmyeloablative Chemotherapy in Patients With Hemoglobinopathies

Phase 2
18 Years
Not Enrolling
Hemoglobinopathies, Anemia, Sickle Cell, Hemoglobin SC Disease, Thalassemia, Thalassemia Major

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Trial Information

Allogeneic Stem Cell Transplantation Following Nonmyeloablative Chemotherapy in Patients With Hemoglobinopathies

Hemoglobinopathies, such as sickle cell disease and thalassemia major, are genetic diseases
associated with significant morbidity and premature death. Allogeneic bone marrow
transplantation (BMT) is the only potential cure for severe hemoglobinopathies. Typical
regimens have used high doses of chemotherapy or chemo-radiotherapy to ablate recipient
hematopoiesis and to prevent graft rejection. The widespread use of this treatment has been
limited by toxicity, risk of end-organ damage, and donor availability. This study will use
a nonmyeloablative regimen of fludarabine and busulfan to attempt to generate consistent
engraftment with donor hematopoietic stem cells in patients with severe hemoglobinopathy.

G-CSF mobilization of the donor's peripheral blood white blood cells will precede donor
apheresis. A nonmyeloablative conditioning regimen of fludarabine and busulfan will be
administered to patients prior to allogeneic peripheral blood stem cell infusions. FK506
and prednisone will be administered for graft versus host disease (GVHD) prophylaxis.
Patients will be evaluated for engraftment, donor: host hematopoietic chimerism, toxicity,
and hemoglobinopathy.

Inclusion Criteria

Inclusion criteria:

- All patients must:

- Have related donors who are identical at 6 human leukocyte antigens (HLA) loci
(A, B and DR) by molecular typing

- Have a performance status from 0-2

- Give written informed consent

- Patients with sickle cell disease should have 1 or more of the following:

- Acute chest syndrome requiring recurrent hospitalization or exchange transfusion

- Nonhemorrhagic stroke or central nervous system event lasting longer than 24

- Recurrent vaso-occlusive pain (2 episodes or more per year) or recurrent

- Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration
rate 30-50 percent of normal predicted value)

- Bilateral proliferative retinopathy and major visual impairment in at least 1

- Osteonecrosis of multiple joints

- Patients with thalassemia should have 1 or more of the following:

- Transfusion dependence, defined as a transfusion requirement of greater than or
equal to 6 units of packed red blood cells over the past 12 months

- Iron overload, defined as serum ferritin greater than 500 mcg/L in the absence
of infection or biopsy-proven iron overload

- Presence of 2 or more alloantibodies against red cell antigens

Exclusion criteria:

- Pregnancy

- Acute hepatitis (transaminases greater than 3 times the normal value)

- Cardiac ejection fraction less than 30 percent

- Severe renal impairment (glomerular filtration rate less than 30 percent of predicted
normal value)

- Severe residual functional neurologic impairment (other than hemiplegia alone)

- Seropositivity for the human immunodeficiency virus (HIV)

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Evidence of engraftment of donor hematopoietic cells following administration of low doses of busulfan and fludarabine

Outcome Time Frame:

Throughout study

Safety Issue:


Principal Investigator

Catherine J. Wu, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Dana Farber Cancer Institute/Harvard Medical School


United States: Federal Government

Study ID:

DAIT DF/HCC 01-098



Start Date:

September 2001

Completion Date:

November 2003

Related Keywords:

  • Hemoglobinopathies
  • Anemia, Sickle Cell
  • Hemoglobin SC Disease
  • Thalassemia
  • Thalassemia Major
  • Anemia
  • Beta-Thalassemia
  • Anemia, Sickle Cell
  • Hemoglobin SC Disease
  • Hemoglobinopathies
  • Thalassemia



Dana-Farber Cancer Institute/Harvard Cancer Center, Brigham and Women's Hospital and Massachusetts General Hospital Boston, Massachusetts  02115