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In Vitro Studies

Ex vivo expansion of megakaryocyte precursor cells in autologous stem cell transplantation for relapsed malignant lymphoma

Bone Marrow Transplantation volume 34, pages 1089–1093 (2004)Cite this article

Summary:

To evaluate the impact of ex vivo expanded megakaryocyte (MK) progenitors on high-dose chemotherapy-induced thrombocytopenia, we conducted a phase II study in 10 patients with relapsed lymphoma. Two fractions of peripheral blood progenitor cells (PBPC) were cryopreserved, one with enough cells for at least 2 × 106 CD34+ cells/kg and a second obtained after CD34+ selection. Ten days before autologous stem cell transplantation, the CD34+ fraction was cultured with MGDF+SCF for 10 days. After BEAM (BCNU, cyclophosphamide, cytarabine, and melphalan) chemotherapy, patients were reinfused with standard PBPC and ex vivo expanded cells. No toxicity was observed after reinfusion. The mean fold expansion was 9.27 for nucleated cells, 2 for CD34+ cells, 676 for CD41+ cells, and 627 for CD61+ cells. The median date of platelet transfusion independence was day 8 (range: 7–12). All patients received at least one platelet transfusion. In conclusion, ex vivo expansion of MK progenitors was feasible and safe, but this procedure did not prevent BEAM-induced thrombocytopenia. Future studies will determine if expansion of higher numbers of CD34+ cells towards the MK-differentiation pathway will translate into a functional effect in terms of shortening of BEAM-induced thrombocytopenia.

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References

  1. Westermann AM, Holtkamp MM, Linthorst GA et al. At home management of aplastic phase following high-dose chemotherapy with stem-cell rescue for haematological and non- haematological malignancies. Ann Oncol 1999; 10: 511–517.

    Article  CAS  Google Scholar 

  2. Archimbaud E, Ottmann OG, Yin JA et al. A randomised, double-blind, placebo-controlled study with pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) as an adjunct to chemotherapy for adults with de novo acute myeloid leukaemia. Blood 1999; 94: 3694–3701.

    CAS  PubMed  Google Scholar 

  3. Norol F, Drouet M, Mathieu J et al. Ex vivo expanded mobilized peripheral blood CD34+ cells accelerate hematologic recovery in a baboon model of autologous transplantation. Br J Haematol 2000; 109: 162–172.

    Article  CAS  Google Scholar 

  4. Brugger W, Mocklin W, Heimfeld S et al. Ex vivo expansion of enriched peripheral blood CD34+ progenitor cells by stem cell factor, interleukin-1 beta (IL-1 beta), IL-6, IL-3, interferon-gamma, and erythropoietin. Blood 1993; 81: 2579–2584.

    CAS  Google Scholar 

  5. Henschler R, Brugger W, Luft T et al. Maintenance of transplantation potential in ex vivo expanded CD34(+)-selected human peripheral blood progenitor cells. Blood 1994; 84: 2898–2903.

    CAS  PubMed  Google Scholar 

  6. David S, Boiron JM, Dupouy M et al. Expansion of blood CD34+ cells: committed precursor expansion does not affect immature hematopoietic progenitors. J Hematother 1997; 6: 151–158.

    Article  CAS  Google Scholar 

  7. Widmer L, Pichert G, Jost LM, Stahel RA . Fate of contaminating t(14; 18)+ lymphoma cells during ex vivo expansion of CD34-selected hematopoietic progenitor cells. Blood 1996; 88: 3166–3175.

    CAS  Google Scholar 

  8. Stiff P, Chen B, Franklin W et al. Autologous transplantation of ex vivo expanded bone marrow cells grown from small aliquots after high-dose chemotherapy for breast cancer. Blood 2000; 95: 2169–2174.

    CAS  Google Scholar 

  9. Yao M, Fouillard L, Lemoine FM et al. Ex vivo expansion of CD34-positive peripheral blood progenitor cells from patients with non-Hodgkin's lymphoma: no evidence of concomitant expansion of contaminating bcl2/JH-positive lymphoma cells. Bone Marrow Transplant 2000; 26: 497–503.

    Article  CAS  Google Scholar 

  10. Holyoake TL, Alcorn MJ, Richmond L et al. CD34 positive PBPC expanded ex vivo may not provide durable engraftment following myeloablative chemoradiotherapy regimens. Bone Marrow Transplant 1997; 19: 1095–1101.

    Article  CAS  Google Scholar 

  11. McNiece I, Jones R, Cagnoni P et al. Ex-vivo expansion of hematopoietic progenitor cells: preliminary results in breast cancer. Hematol Cell Ther 1999; 41: 82–86.

    Article  CAS  Google Scholar 

  12. Norol F, Vitrat N, Cramer E et al. Effects of cytokines on platelet production from blood and marrow CD34+ cells. Blood 1998; 91: 830–843.

    CAS  PubMed  Google Scholar 

  13. van den Oudenrijn S, de Haas M, Calafat J et al. A combination of megakaryocyte growth and development factor and interleukin-1 is sufficient to culture large numbers of megakaryocytic progenitors and megakaryocytes for transfusion purposes. Br J Hematol 1999; 106: 553–563.

    Article  CAS  Google Scholar 

  14. Drayer AL, Sibinga CT, Blom NR et al. The in vitro effects of cytokines on expansion and migration of megakaryocyte progenitors. Br J Haematol 2000; 109: 776–784.

    Article  CAS  Google Scholar 

  15. Blair A, Baker CL, Pamphilon DH, Judson PA . Ex vivo expansion of megakaryocyte progenitor cells from normal bone marrow and peripheral blood and from patients with haematological malignancies. Br J Haematol 2002; 116: 912–919.

    Article  Google Scholar 

  16. Bertolini F, Battaglia P, Pedrazzoli GA et al. Megakaryocyte progenitors can be generated ex vivo and safely administered to autologous peripheral blood progenitor cell transplant recipients. Blood 1997; 89: 2679–2688.

    CAS  Google Scholar 

  17. Williams SF, Lee WJ, Bender JG et al. Selection and expansion of peripheral blood CD34+ cells in autologous stem cell transplantation for breast cancer. Blood 1996; 87: 1687–1691.

    CAS  Google Scholar 

  18. Engelhardt M, Douville J, Behringer D et al. Hematopoietic recovery of ex vivo perfusion culture expanded bone marrow and unexpanded peripheral blood progenitors after myeloablative chemotherapy. Bone Marrow Transplant 2001; 27: 249–259.

    Article  CAS  Google Scholar 

  19. Paquette RL, Dergham ST, Karpf E et al. Culture conditions affect the ability of ex vivo expanded peripheral blood progenitor cells to accelerate hematopoietic recovery. Exp Hematol 2002; 30: 374–380.

    Article  CAS  Google Scholar 

  20. Scheding S, Bergmann M, Rathke G et al. Additional transplantation of ex-vivo generated Megakaryocytic cells after high-dose chemotherapy: results of a pilot study. Blood 2002; 100: 3291 (abstract).

    Google Scholar 

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Author notes

  1. D Decaudin and J-M Vantelon: Equal contribution as first authors

  2. A G Turhan and C Boccaccio: Equal contribution as last authors

Authors and Affiliations

  1. Department of Clinical Hematology, Institut Curie, Paris, France

    D Decaudin & F Némati

  2. Department of Clinical Hematology, Institut Gustave Roussy, Villejuif, France

    J-M Vantelon & J-H Bourhis

  3. Inserm U362, Hématopoiëse et Cellules Souches, Institut Gustave Roussy, Villejuif, France

    F Farace, M-L Bonnet, M Guillier & A G Turhan

  4. Department of Clinical Biology, Cell Therapy Unit, Translational Research and Cell Therapy Laboratories, Institut Gustave Roussy, Villejuif, France

    F Farace, M-L Bonnet, M Guillier, N Greissenger, M-C Marracho, A G Turhan & C Boccaccio

  5. Department of Transfusion, Institut Curie, Paris, France

    S Assari

  6. Department of Clinical Biology, Laboratoire d'Hématologie, IGR, Villejuif, France

    A-L Bennaceur

  7. Department of Pediatric Oncology, Institut Curie, Paris, France

    J Michon

Authors
  1. D Decaudin
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  2. J-M Vantelon
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  4. F Farace
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  6. M Guillier
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  7. N Greissenger
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  8. M-C Marracho
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  9. S Assari
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  10. A-L Bennaceur
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  11. F Némati
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  12. J Michon
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  13. A G Turhan
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  14. C Boccaccio
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Corresponding author

Correspondence to A G Turhan.

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Decaudin, D., Vantelon, JM., Bourhis, JH. et al. Ex vivo expansion of megakaryocyte precursor cells in autologous stem cell transplantation for relapsed malignant lymphoma. Bone Marrow Transplant 34, 1089–1093 (2004). https://doi.org/10.1038/sj.bmt.1704675

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  • DOI: https://doi.org/10.1038/sj.bmt.1704675

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