HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity

Inclusion Criteria:

• Patient Inclusion Criteria for Sickle Cell Disease
• Patients at least one year of age to less than or equal to 21 years of age with (Sickle Cell Disease-SS or Sickle Cell-S-β-Thalassemia and with one or more of the following disease complications:
• Development of stroke on chronic transfusion protocol.
• Allosensitization on chronic transfusion therapy
• Impaired neuropsychological function and abnormal MRI scan
• Abnormal Transcranial Doppler studies
• Acute chest syndrome (2 to 3 episodes of acute chest syndrome in last 3 to 4 years).
• Ferritin level < 1500 mg/ml
• Recurrent painful priapism; 3-4 episodes/year requiring intervention.
• Recurrent vaso-occlusive crisis of at least 3 to 4 episodes/year.
• Osteonecrosis of multiple bones with documented destructive changes.
• Signed informed consent
• Patients physically and psychologically capable of undergoing transplantation and a period of strict isolation.
• Ferritin < 1500
• Liver Iron Concentration < 6mg/g

Patient Inclusion Criteria for β Thalassemia major Patients less than or equal to 21 years of age with B- Thalassemia major on routine monthly transfusion protocol or with one or more of the following complications;

1. Hepatomegaly.
2. Liver biopsy revealing evidence of portal fibrosis as A) Mild B) Moderate
3. Ferritin level≤ 1500ng/ml
4. Liver Iron Concentration (LIC) < 6mg/g

Exclusion Criteria:

• Exclusion Criteria for Both Sickle Cell and β Thalassemia Major Patient
• HIV positive result confirmed by Western Blot.
• Pregnancy (Pregnancy testing for females of child-bearing age will be performed and those with a positive serum β-Human Chorionic Gonadotropin will be excluded) and lactating females.
• Creatinine greater than two times the upper limit of normal for the laboratory,
• Pulmonary disease with FVC, FEV1 or DLCO parameters < 50% predicted (corrected for hemoglobin) or stage 3 or 4 sickle lung disease.
• Cardiac insufficiency or coronary artery disease requiring treatment
• Active infection requiring systemic antibiotic therapy with antibacterial, antifungal or antiviral agents
• Lansky performance score <70%- (Appendix B)
• Acute hepatitis/biopsy evidence of cirrhosis.
• Pulmonary Hypertension