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


Authors: Boulad, F.; Wang, X.; Qu, J.; Taylor, C.; Ferro, L.; Karponi, G.; Bartido, S.; Giardina, P.; Heller, G.; Prockop, S. E.; Maggio, A.; Sadelain, M.; Riviere, I.
Article Title: Safe mobilization of CD34+ cells in adults with β-thalassemia and validation of effective globin gene transfer for clinical investigation
Abstract: 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. © 2014 by The American Society of Hematology.
Keywords: adult; clinical article; protein expression; human cell; hydroxyurea; nonhuman; mouse; cd34 antigen; neutrophil count; animal experiment; animal model; hemoglobin; hemoglobin blood level; gene transfer; hemoglobin beta chain; lentivirus vector; globin gene; stem cell mobilization; anxiety; hematopoietic stem cell; leukocyte count; granulocyte colony stimulating factor; expression vector; thalassemia major; leukapheresis; good manufacturing practice; human; priority journal; article; hemoglobin alpha chain
Journal Title: Blood
Volume: 123
Issue: 10
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2014-03-06
Start Page: 1483
End Page: 1486
Language: English
DOI: 10.1182/blood-2013-06-507178
PROVIDER: scopus
PMCID: PMC3945860
PUBMED: 24429337
DOI/URL:
Notes: Export Date: 1 May 2014 -- CODEN: BLOOA -- Source: Scopus
Altmetric Score
MSK Authors
  1. Farid Boulad
    245 Boulad
  2. Glenn Heller
    291 Heller
  3. Susan E Prockop
    160 Prockop
  4. Michel W J Sadelain
    452 Sadelain
  5. Isabelle C Riviere
    161 Riviere
  6. Xiuyan Wang
    62 Wang
  7. Shirley M Bartido
    34 Bartido
  8. Clare Taylor
    16 Taylor
  9. Leda C Ferro
    4 Ferro
  10. Jinrong Qu
    13 Qu