Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Autografting

Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution in non-Hodgkin's lymphoma (NHL): results of Japanese phase II study

Summary:

The purging efficacy of positive selection of autologous CD34+ PBSC with a clinical scale method of magnetic-activated cell sorting system (CliniMACS) was investigated in 48 patients with non-Hodgkin’s lymphoma (NHL). The median purity and recovery rate of the CD34+ cells post-selection were 93.3% (range 32.6–99.3) and 72.2% (range 20.5–309.8), respectively. The real-time PCR method to detect the patient-specific monoclonal immunoglobulin heavy chain gene rearrangement (minimal residual tumor; MRT) and CD19 and CD20 positivities were used for the detection of contaminating NHL cells before and after CD34+ selection. After selection, the median (range) depletion rate of MRT was 2.53 (1.52–4.78) log, and that of CD19+ cell and CD20+ cell was 2.46 (0.74–3.64) log and 2.32 (0.40–4.01) log, respectively. In 41 patients, high-dose chemotherapy was performed, followed by the transplantation of the isolated CD34+ cells. Rapid neutrophil recovery as well as platelet recovery was seen with a median time to reach 0.5 × 109/l neutrophils of 10 days (range 8–13) and 20 × 109/l platelets of 14 days (range 10–34), respectively. The present study demonstrated that CliniMACS is a highly effective positive selection method and a high purging efficacy could be obtained without compromising the hematopoietic reconstitution capacity of the graft in NHL patients undergoing high-dose chemotherapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Philip T, Guglielmi C, Hagenbeek A et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin’s lymphoma. N Engl J Med 1995; 333: 1540–1545.

    Article  CAS  PubMed  Google Scholar 

  2. Schenkein DP, Roitman D, Miller KB et al. A phase II multi-center trial of high-dose sequential chemotherapy and peripheral blood stem cell transplantation as initial therapy for patients with high-risk non-Hodgkin’s lymphoma. Biol Blood Marrow Transplant 1997; 3: 210–216.

    CAS  PubMed  Google Scholar 

  3. Haioun C, Lepage E, Gisselbrecht C et al. Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin’s lymphoma: final analysis of the prospective LNH 87-2 protocol – A groupe d'Etude des lymphomas de l'Adulte study. J Clin Oncol 2000; 18: 3025–3030.

    Article  CAS  PubMed  Google Scholar 

  4. Shipp MA, Abeloff MD, Antman KH et al International consensus conference on high-dose therapy with hematopoietic stem cell transplantation in aggressive non-Hodgkin’s lymphomas: report of the jury. J Clin Oncol 1999; 17: 423–429.

    Article  CAS  PubMed  Google Scholar 

  5. Sharp JG, Joshi SS, Armitage JO et al. Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique. Blood 1992; 79: 1074–1080.

    CAS  PubMed  Google Scholar 

  6. Ratanatharathorn V, Uberti J, Karanes C et al. Prospective comparative trial of autologous versus allogeneic bone marrow transplantation in patinents with non-Hodgkin’s lymphoma. Blood 1994; 84: 1050–1055.

    CAS  PubMed  Google Scholar 

  7. Miltenyi S, Muller W, Weichel W et al. High-gradient magnetic cell separation with MACS. Cytometory 1990; 11: 231–238.

    Article  CAS  Google Scholar 

  8. Miltenyi S, Guth S, Radbruch A et al. Isolation of CD34+ hematopoietic progenitor cells by high-gradient magnetic cell sorting (MACS). In: Miltenyi S, Thiel A (eds). Hematopietic Stem Cells: The Mulhouse Manual. Alphamed Press: Dayton, OH, USA, 1994, pp 201–213.

    Google Scholar 

  9. Chou T, Ishiguro T, Imajo K et al. A multicenter early phase II study of high-dose chemotherapy with autologous peripheral blood stem cell transplantation for treatment of intermediate grade non-Hodgkin's lymphoma. Jpn J Clin Hematol 1999; 40: 1058–1067.

    CAS  Google Scholar 

  10. Cheson BD, Horning SJ, Coiffier B et al Report of an International Workshop to standardize response criteria for non-Hodgkin's lymphomas. J Clin Oncol 1999; 17: 1244–1253.

    Article  CAS  PubMed  Google Scholar 

  11. Richel DJ, Johnsen HE, Canon J et al. Highly purified CD34+ cells isolated using magnetically activated cell selection provide rapid engraftment following high-dose chemotherapy in breast cancer patients. Bone Marrow Transplant 2000; 25: 243–249.

    Article  CAS  PubMed  Google Scholar 

  12. Shpall EJ, LeMaistre CF, Holland K et al. A prospective randomized trial of buffy coat versus CD34-selected autologous bone marrow support in high-risk breast cancer patients receiving high-dose chemotherapy. Blood 1997; 90: 4313–4320.

    CAS  PubMed  Google Scholar 

  13. Voso MT, Hohaus S, Moos M et al. Autografting with CD34+ peripheral blood stem cells: retained engraftment capability and reduced tumour cell content. Br J Haematol 1999; 104: 382–391.

    Article  CAS  PubMed  Google Scholar 

  14. Henon PR, Liang H, Beckwirth G et al Comparison of hemopoietic and immune recovery after autologous bone marrow or blood stem cell transplants. Bone Marrow Transplant 1992; 9: 285–291.

    CAS  PubMed  Google Scholar 

  15. Roberts MM, To LB, Gillis D et al. Immune reconstitution following peripheral blood stem cell transplantation, autologous bone marrow transplantation and allogeneic bone marrow transplantation. Bone Marrow Transplant 1993; 12: 469–475.

    CAS  PubMed  Google Scholar 

  16. Miyamoto T, Gondo H, Miyoshi Y . Early viral complications following CD34-selected autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma. Br J Haematol 1998; 100: 348–350.

    Article  CAS  PubMed  Google Scholar 

  17. Holmberg LA, Boeckh M, Hooper H et al Increased incidence of Cytomegalovirus disease after autologous CD34-selected peripheral blood stem cell transplantation. Blood 1999; 94: 4029–4035.

    CAS  PubMed  Google Scholar 

  18. Friedman J, Lazarus HM, ON Koc . Autologous CD34+ enriched peripheral blood progenitor cell (PBPC) transplantation is associated with higher morbidity in patients with lymphoma when compared to unmanipulated PBPC transplantation. Bone Marrow Transplant 2000; 26: 831–836.

    Article  CAS  PubMed  Google Scholar 

  19. Paulus U, Dreger P, Viehmann K et al. Purging peripheral blood progenitor cellgrafts from lymphoma cells: quantitative comprison of immunomagnetic CD34+ selection systems. Stem Cells 1997; 15: 297–304.

    Article  CAS  PubMed  Google Scholar 

  20. Freedman AS, Neuberg D, Mauch P et al. Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma. Blood 1999; 94: 3325–3333.

    CAS  PubMed  Google Scholar 

  21. Horning SJ, Negrin RS, Hoppe RT et al. High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete remission: results of a phase II clinical trial. Blood 2001; 97: 404–409.

    Article  CAS  PubMed  Google Scholar 

  22. Schouten HC, Qian W, Kvaloy S et al. High-dose therapy improves progression-free survival and survival in relapsed follicular non-Hodgkin’s lymphoma: results form the randomized European CUP trial. J Clin Oncol 2003; 21: 3918–3927.

    Article  CAS  PubMed  Google Scholar 

  23. Magni M, Di Nicola M, Devizzi L et al. Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion. Blood 2000; 96: 864–869.

    CAS  PubMed  Google Scholar 

  24. Flohr T, Hess G, Kolbe K et al. Rituximab in vivo purging is safe and effective in combination with CD34-positive selected autologous stem cell transplantation for salvage therapy in B-NHL. Bone Marrow Transplant 2002; 29: 769–775.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge Kirin Brewery Co. Ltd, Japan for providing the CliniMACS device and support throughout this study.

Author information

Authors and Affiliations

Authors

Consortia

Corresponding author

Correspondence to T Chou.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Imai, Y., Chou, T., Tobinai, K. et al. Isolation and transplantation of highly purified autologous peripheral CD34+ progenitor cells: purging efficacy, hematopoietic reconstitution in non-Hodgkin's lymphoma (NHL): results of Japanese phase II study. Bone Marrow Transplant 35, 479–487 (2005). https://doi.org/10.1038/sj.bmt.1704819

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704819

Keywords

Search

Quick links