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

Blood. 2014 Mar 6;123(10):1483-6. doi: 10.1182/blood-2013-06-507178. Epub 2014 Jan 15.


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 × 10(6) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Colony-Forming Units Assay
  • Disease Models, Animal
  • Erythroid Precursor Cells / metabolism
  • Gene Expression
  • Gene Transfer Techniques*
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Hematopoietic Stem Cell Mobilization*
  • Hematopoietic Stem Cell Transplantation*
  • Heterografts
  • Humans
  • Mice
  • Transduction, Genetic
  • beta-Globins / biosynthesis
  • beta-Globins / genetics*
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / metabolism
  • beta-Thalassemia / therapy*


  • Antigens, CD34
  • beta-Globins

Associated data