Blood Journal
Leading the way in experimental and clinical research in hematology

Brief Report
Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation

  1. Farid Boulad1,2,
  2. Xiuyan Wang1,3,4,
  3. Jinrong Qu4,
  4. Clare Taylor4,
  5. Leda Ferro4,
  6. Garyfalia Karponi4,
  7. Shirley Bartido4,
  8. Patricia Giardina5,
  9. Glenn Heller6,
  10. Susan E. Prockop2,
  11. Aurelio Maggio7,
  12. Michel Sadelain1,3, and
  13. Isabelle Rivière1,3,4
  1. 1Center for Cell Engineering,
  2. 2Bone Marrow Transplant Service, Department of Pediatrics,
  3. 3 Molecular Pharmacology and Chemistry Program, and
  4. 4Cell Therapy and Cell Engineering Facility, Memorial Sloan-Kettering Cancer Center, New York, NY;
  5. 5Department of Pediatrics, New York-Presbyterian Hospital-Weill Cornell Medical College, New York, NY;
  6. 6Department of Epidemiology & Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY; and
  7. 7Ospedale V. Cervello, Palermo, Italy

Key Points

  • Safe mobilization of CD34+ cells in adults with β-thalassemia and effective transduction with a globin vector under cGMP conditions.

  • Stable vector copy number and β-globin expression in BFU-Es derived from engrafted CD34+ HPCs 6 months post-transplant in NSG mice.


We conducted a pilot trial to investigate the safety and effectiveness of mobilizing CD34+ hematopoietic progenitor cells (HPCs) in adults with β-thalassemia major. We further assessed whether thalassemia patient CD34+ HPCs could be transduced with a globin lentiviral vector under clinical conditions at levels sufficient for therapeutic implementation. All patients tolerated granulocyte colony-stimulating factor well with minimal side effects. All cell collections exceeded 8 × 106 CD34+ cells/kg. Using clinical grade TNS9.3.55 vector, we demonstrated globin gene transfer averaging 0.53 in 3 validation runs performed under current good manufacturing practice conditions. Normalized to vector copy, the vector-encoded β-chain was expressed at a level approximating normal hemizygous protein output. Importantly, stable vector copy number (0.2-0.6) and undiminished vector expression were obtained in NSG mice 6 months posttransplant. Thus, we validated a safe and effective procedure for β-globin gene transfer in thalassemia patient CD34+ HPCs, which we will implement in the first US trial in patients with severe inherited globin disorders. This trial is registered at as #NCT01639690.

  • Submitted June 12, 2013.
  • Accepted January 1, 2014.
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