Safety and Efficacy of Gene Modified Autologous Hematopoietic Stem Cells to Treat Transfusion-dependent Beta-thalassemia

Exclusion Criteria

• •1. Availability of voluntary, fully HLA-matched hematopoietic cell donors, unless recommended for inclusion by the Monitoring Committee.
• •2. HIV-1 and HIV-2 were positive, and / or HTLV-1, HTLV-2 and VSV-G antibodies were positive.
• •3. An active bacterial, viral, fungal or parasitic infection.
• •4. Contraindicated for the extraction of bone marrow under anesthesia.
• •5. Any malignancy, myeloproliferative, or immunodeficient disease and relevant medical history.
• •6. Peripheral blood white blood cell (WBC) count \< 3×10\^9/L or platelet count \< 120×10\^9/L.
• •7. A history of allo-transplantation.
• •8. Erythropoietin was used within 3 months prior to HSC cell collection.
• •9. Immediate family members with known or suspected familial cancer syndromes (including but not limited to breast, colorectal, ovarian, prostate, and pancreatic cancers).
• •10. Subjects with a diagnosis of major mental illness may had a serious disability to participate in the study.
• •11. Active recurrent malaria.
• •12. Had autoimmune diseases that may make blood transfusions difficult.
• •13. History of major organ injury including:
• •Liver disease, transaminase \> 3 times the upper limit of normal. (If the liver biopsy does not reveal evidence of widespread bridging fibrosis, cirrhosis, or acute hepatitis, this indicator will not be used as a criterion for the exclusion); Widely bridging fibrosis, histopathological evidence of acute hepatitis or cirrhosis showed in liver biopsy Heart disease, left ventricular ejection fraction \< 25%; Kidney disease, creatinine clearance \< 30% normal level; Of severe iron overload, confirmed by the study doctor; An heart MRI detection of T2 \* \< 10 ms; Significant pulmonary hypertension needing clinical medical intervention.
• •14. There are bleeding diseases that have not been cured.
• •15. The subject involved with another clinical study in a 30-day screening period.
• •16. Allergic to the research drug and its excipients.
• •17. Prior treatment with any type of gene and/or cell therapy.
• •18. As assessed by the investigator, the subjects or their parents are unable to comply well with the study procedures per protocol.
• •19. Hydroxyurea treatment within 3 months prior to hematopoietic stem cell collection.
• •20. Had diseases that interfere with hematopoietic stem cells collections.
• •21. Any other conditions being ineligible for HSC transplantation determined by the investigator.