Stem Cell Transplant for Hemoglobinopathy

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 testing
  • Acute chest syndrome with a history of recurrent hospitalizations or exchange transfusions
  • 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 eye
  • 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 biopsy
• 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