HSCT For Patients With High Risk Hemoglobinopathies Using Reduced Intensity
Sickle Cell Disease, Beta Thalassemia-Major
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Reduced Intensity Conditioning Regimen
Eligibility Criteria
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;
- Hepatomegaly.
- Liver biopsy revealing evidence of portal fibrosis as A) Mild B) Moderate
- Ferritin level≤ 1500ng/ml
- 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
Sites / Locations
- Cohen Children's Medical Center of New York
Arms of the Study
Arm 1
Experimental
Reduced Intensity Regimen
Administration of reduced doses of alemtuzumab (Campath-IH) IV 3mg test dose on Day -20 followed by daily dose of 10mg/dose on Day -19 to Day -17 for patients <10yrs or a daily dose of 15mg/dose on Day -19 to Day -17 for patients > 10yrs. Fludarabine 35mg/m2 daily for 4 days on Day -7 to Day -4. Melphalan 70mg/m2 daily for 2 days on Day -3 and Day -2. On Day -1 Cyclosporine OR Tacrolimus will be initiated along with Mycophenolate Mofetil as a graft vs host disease prophylaxis. On Day 0 the Human Leukocyte Antigen (HLA) matched or mismatched Hematopoietic Stem Cells from either the related or unrelated donor will be infused.