ß-Thalassemia Major With Autologous CD34+ Hematopoietic Progenitor Cells Transduced With TNS9.3.55 a Lentiviral Vector Encoding the Normal Human ß-Globin Gene

Inclusion Criteria

• •Subjects must be 18 years or older
• •Subjects may be of either gender or of any ethnic background
• •Subjects must have a confirmed diagnosis of ß-thalassemia major and have been enrolled in a hypertransfusion program with a confirmed annual transfusion of ≥100 mL/kg/yr but \< 200 mL/kg/yr, AND ≥ 8 transfusions of blood per year over a minimum of two years.
• •Patients must NOT have an HLA-matched sibling
• •Patients must be off hydroxyurea (HU) or erythropoietin (EPO) treatment for at least three months prior to entry onto the study
• •Subjects must have a performance score of Karnofsky ≥70% at the time of entry into the study.
• •Subjects must have liver iron value of \< 15 mg/g/dry weight Iron quantitation may be performed by imaging such as T2\*MRI or by biopsy
• •Subjects must have no evidence of cirrhosis\*\* of the liver. Fibrosis of the liver can be tested by Fibroscan (47, 48, 49), or by liver biopsy. These should be performed within approximately a one year period prior to entry onto the study.
• •Subjects with an evaluation of cardiac function indicating:
• •normal function on MUGA scan (Multiple Gated Acquisition scan) or other methodology.
• •And
• •Patients must have a left ventricular ejection fraction (LVEF) of ≥ 60% and/or T2\*MRI cardiac evaluation with T2\* ≥20 milliseconds
• •Subjects with asymptomatic pulmonary function based on Lung Diffusion Testing DLCO Test DLCO ≥ 50% of predicted (corrected for hemoglobin)
• •Subjects with a determination of renal function based on: serum creatinine \< than or = to 1.5 mg/dL or if serum creatinine is outside the normal range, then CrCl \> 60-ml/min/1.73 m2
• •Subjects must have adequate hepatic function based on:
• •\< 3 x ULN ALT and
• •\< 2.0 total serum bilirubin (unless secondary to hemolysis)
• •Patients must be available for follow-up evaluations at 30, 60, 180 days post BMT and yearly thereafter indefinitely.
• •* The possibility of unrelated donor stem cell transplantation will be discussed with patients, and a "preliminary" search for an unrelated donor may be done at the request of the patient. However, the finding of a potential HLA-matched unrelated donor will not exclude the patient from participating into this trial).