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.

  • Review
  • Published:

Has allogeneic stem cell cryopreservation been given the ‘cold shoulder’? An analysis of the pros and cons of using frozen versus fresh stem cell products in allogeneic stem cell transplantation

Bone Marrow Transplantation volume 38, pages 399–405 (2006)Cite this article

Abstract

Donor stem cells for allogeneic transplant traditionally are collected and transfused ‘fresh’ into the recipient on the day of transplant; alternatively such cells can be collected in advance and cryopreserved until needed. Most centers favor the former approach based on theoretical concerns that cryopreservation and thawing may worsen clinical outcomes. Limited published data from single institution retrospective studies show no significant impairment of engraftment or reduced day 100 survival for cryopreserved bone marrow recipients. There are no reported outcomes for recipients of cryopreserved peripheral blood allografts. Use of cryopreserved stem cells is associated with a higher incidence of adverse events (transfusion reactions, bacterial graft contamination and collection of grafts which are not utilized). Conversely, use of cryopreserved grafts introduces a greater flexibility into a stressed healthcare system and results in a more streamlined experience for the donor. Some data suggest that transplantation with a cryopreserved product may lower the incidence of acute graft-versus-host disease. We compare the pros and cons of using ‘fresh’ versus cryopreserved stem cell products for allogeneic transplantation and suggest that the current standard of using ‘fresh’ products may not be warranted. We also suggest future areas of exploration to better elucidate this issue.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Similar content being viewed by others

References

  1. Shinkoda Y, Ijichi O, Tanabe T, Ishikawa S, Kamitamari A, Nishikawa T et al. Identical reconstitution after bone marrow transplantation in twins who received fresh and cryopreserved grafts harvested at the same time from their older brother. Clin Transplant 2004; 18: 743–747.

    Article  Google Scholar 

  2. Eckardt JR, Roodman GD, Boldt DH, Clark GM, Alvarez R, Page C et al. Comparison of engraftment and acute GVHD in patients undergoing cryopreserved or fresh allogeneic BMT. Bone Marrow Transplant 1993; 11: 125–131.

    CAS  PubMed  Google Scholar 

  3. Lasky LC, Van Buren N, Weisdorf DJ, Filipovich A, McGlave P, Kersey JH et al. Successful allogeneic cryopreserved marrow transplantation. Transfusion 1989; 29: 182–184.

    Article  CAS  Google Scholar 

  4. Stockschlader M, Hassan HT, Krog C, Kruger W, Loliger C, Horstman M et al. Long-term follow-up of leukaemia patients after related cryopreserved allogeneic bone marrow transplantation. Br J Haematol 1997; 96: 382–386.

    Article  CAS  Google Scholar 

  5. Stockschlader M, Kruger W, Kroschke G, Zeller W, Hoffknecht M, Loliger C et al. Use of cryopreserved bone marrow in allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 15: 569–572.

    CAS  PubMed  Google Scholar 

  6. Stockschlader M, Kruger W, Tom Dieck A, Horstmann M, Altnoder M, Loliger C et al. Use of cryopreserved bone marrow in unrelated allogeneic transplantation. Bone Marrow Transplant 1996; 17: 197–199.

    CAS  PubMed  Google Scholar 

  7. Stockschlader M, Loliger C, Kruger W, Zeller W, Heyll A, Schonrock-Nabulsi P et al. Transplantation of allogeneic rhG-CSF mobilized peripheral CD34+ cells from an HLA-identical unrelated donor. Bone Marrow Transplant 1995; 16: 719–722.

    CAS  PubMed  Google Scholar 

  8. Sohn SK, Jung JT, Kim DH, Lee NY, Seo KW, Chae YS et al. Prophylactic growth factor-primed donor lymphocyte infusion using cells reserved at the time of transplantation after allogeneic peripheral blood stem cell transplantation in patients with high-risk hematologic malignancies. Cancer 2002; 94: 18–24.

    Article  CAS  Google Scholar 

  9. Robinson SN, Freedman AS, Neuberg DS, Nadler LM, Mauch PM . Loss of marrow reserve from dose-intensified chemotherapy results in impaired hematopoietic reconstitution after autologous transplantation: CD34(+), CD34(+)38(−), and week-6 CAFC assays predict poor engraftment. Exp Hematol 2000; 28: 1325–1333.

    Article  CAS  Google Scholar 

  10. Tricot G, Jagannath S, Vesole D, Nelson J, Tindle S, Miller L et al. Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients. Blood 1995; 85: 588–596.

    CAS  PubMed  Google Scholar 

  11. Weaver CH, Hazelton B, Birch R, Palmer P, Allen C, Schwartzberg L et al. An analysis of engraftment kinetics as a function of the CD34 content of peripheral blood progenitor cell collections in 692 patients after the administration of myeloablative chemotherapy. Blood 1995; 86: 3961–3969.

    CAS  PubMed  Google Scholar 

  12. Feugier P, Bensoussan D, Girard F, Alla F, Schuhmacher A, Latger-Cannard V et al. Hematologic recovery after autologous PBPC transplantation: importance of the number of postthaw CD34+ cells. Transfusion 2003; 43: 878–884.

    Article  Google Scholar 

  13. Manilay JO, Sykes M . Natural killer cells and their role in graft rejection. Curr Opin Immunol 1998; 10: 532–538.

    Article  CAS  Google Scholar 

  14. Martin PJ . Donor CD8 cells prevent allogeneic marrow graft rejection in mice: potential implications for marrow transplantation in humans. J Exp Med 1993; 178: 703–712.

    Article  CAS  Google Scholar 

  15. Marmont AM, Horowitz MM, Gale RP, Sobocinski K, Ash RC, van Bekkum DW et al. T-cell depletion of HLA-identical transplants in leukemia. Blood 1991; 78: 2120–2130.

    CAS  PubMed  Google Scholar 

  16. Group SCTC. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol 2005; 23: 5074–5087.

  17. Ludgate ME, Dryden PR, Weetman AP, McGregor AM . T-cell subset analysis of cryopreserved human peripheral blood mononuclear cells. Immunol Lett 1983; 7: 119–122.

    Article  CAS  Google Scholar 

  18. Jones HP, Hughes P, Kirk P, Hoy T . T-cell subsets: effects of cryopreservation, paraformaldehyde fixation, incubation regime and choice of fluorescein-conjugated anti-mouse IgG on the percentage positive cells stained with monoclonal antibodies. J Immunol Methods 1986; 92: 195–200.

    Article  CAS  Google Scholar 

  19. Tollerud DJ, Brown LM, Clark JW, Neuland CY, Mann DL, Pankiw-Trost LK et al. Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity. J Clin Lab Anal 1991; 5: 255–261.

    Article  CAS  Google Scholar 

  20. Stroncek DF, Fautsch SK, Lasky LC, Hurd DD, Ramsey NK, McCullough J . Adverse reactions in patients transfused with cryopreserved marrow. Transfusion 1991; 31: 521–526.

    Article  CAS  Google Scholar 

  21. Lazarus HM, Magalhaes-Silverman M, Fox RM, Creger RJ, Jacobs M . Contamination during in vitro processing of bone marrow for transplantation: clinical significance. Bone Marrow Transplant 1991; 7: 241–246.

    CAS  PubMed  Google Scholar 

  22. Rowley SD, Davis J, Dick J, Braine HG, Charache P, Saral R et al. Bacterial contamination of bone marrow grafts intended for autologous and allogeneic bone marrow transplantation. Incidence and clinical significance. Transfusion 1988; 28: 109–112.

    Article  CAS  Google Scholar 

  23. Padley D, Koontz F, Trigg ME, Gingrich R, Strauss RG . Bacterial contamination rates following processing of bone marrow and peripheral blood progenitor cell preparations. Transfusion 1996; 36: 53–56.

    Article  CAS  Google Scholar 

  24. Suzuya H, Watanabe T, Nakagawa R, Watanabe H, Okamoto Y, Onishi T et al. Factors associated with granulocyte colony-stimulating factor-induced peripheral blood stem cell yield in healthy donors. Vox Sang 2005; 89: 229–235.

    Article  CAS  Google Scholar 

  25. Anderlini P, Donato M, Chan KW, Huh YO, Gee AP, Lauppe MJ et al. Allogeneic blood progenitor cell collection in normal donors after mobilization with filgrastim: the M.D. Anderson Cancer Center experience. Transfusion 1999; 39: 555–560.

    Article  CAS  Google Scholar 

  26. Devine SM, Andritsos L, Todt L, Vij R, Bonde J, Hess D et al. A pilot study evaluating the safety and efficacy of AMD3100 for the mobilization and transplantation of HLA-matched sibling donor hematopoietic stem cells in patients with advanced hematological malignancies. ASH Annual Meeting Abstracts 2005; 106: 299.

    Google Scholar 

Download references

Acknowledgements

We would like to thank Dennis Confer, MD and David Avigan, MD for manuscript review and excellent suggestions. We also thank Roberta King, MPH, of the NMDP for her assistance.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology/BMT, Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA

    N V Frey & S C Goldstein

  2. Department of Medicine, Comprehensive Cancer Center of Case Western Reserve University and University Hospitals of Cleveland, Cleveland, OH, USA

    H M Lazarus

Authors
  1. N V Frey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H M Lazarus
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S C Goldstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S C Goldstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frey, N., Lazarus, H. & Goldstein, S. Has allogeneic stem cell cryopreservation been given the ‘cold shoulder’? An analysis of the pros and cons of using frozen versus fresh stem cell products in allogeneic stem cell transplantation. Bone Marrow Transplant 38, 399–405 (2006). https://doi.org/10.1038/sj.bmt.1705462

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1705462

Keywords

This article is cited by

Search

Advanced search

Quick links