Gene Therapy for Beta-Thalassemia Major Using Autologous Hematopoietic Stem Cell Genetically Modified

Exclusion Criteria

• •Having an HLA-matched donor(sibling or of a suitable 10/10 matched unrelated donor).
• •Positivity for HIV (serology or RNA), and/or HbsAg and/or HBV DNA and/or HCV RNA (or negative HCV RNA but on antiviral treatment).
• •Contraindication to anesthesia for bone marrow collection.
• •Severe, bacterial, active viral, or fungal infection, etc.
• •The history of malignant tumor.
• •The white blood cell (WBC) count \<3000/uL and/or platelet count \<100,000/uL exclude hypersplenism factor.
• •Family history of familial cancer syndromes (including but not limited to Hereditary breast and ovarian syndrome, hereditary non-polyp colorectal cancer syndrome, familial adenomatous polyposis).
• •Previous allogeneic bone marrow transplantation.
• •The history of psychosis and any psychiatric disorder.
• •Active substance abuse, drug or alcohol abuse recently.
• •The history of complex allo-immunization which could cause difficulty administering transfusions.
• •Female adults who are pregnant , breast feeding or lack of effective contraception.
• •History of major organ damage including:
• •Severe cerebrovascular disease or cognitive sequelae, including hemiplegia. Severe liver disease with alanine transaminase (ALT) \>3 upper limit of normal. Severe liver cirrhosis or fibrosis on liver biopsy. Heart disease with ejection fraction\<25% or T2\* \<10 ms by magnetic resonance imaging (MRI). Kidney disease with creatinine clearance \<30% normal value. Lung disease, including pulmonary fibrosis, pulmonary arterial hypertension or pulmonary function tests below standard (i.e., pO2\<90 mmHg and/or carbon dioxide diffusion coefficient\<50%). Endocrine disorder including insulin dependent diabetes mellitus, Hyperthyroidism or deficiency, Hyperparathyroidism or deficiency.
• •Participation in another clinical study within 30 days of screening.
• •Subjects with severe iron overload determined by the researchers.
• •Any other situation that unsuitably undergoing hematopoietic stem cell transplantation determined by the physicians or researchers.
• •Presence of chromosomal abnormalities by bone marrow detected.