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.

  • Article
  • Published:

Reduction of DMSO concentration in cryopreservation mixture from 10% to 7.5% and 5% has no impact on engraftment after autologous peripheral blood stem cell transplantation: results of a prospective, randomized study

Abstract

The procedure of autologous peripheral blood stem cell transplantation (autoPBSCT) requires cryopreservation of cells in a mixture containing dimethyl sulfoxide (DMSO). DMSO is necessary to secure cell viability, however, its infusion may be toxic to stem cell recipient. The aim of this study was to prospectively evaluate the impact of DMSO concentration on engraftment after autoPBSCT.

One-hundred-fifty patients were randomly assigned to one of three study arms; their leukapheresis products were cryopreserved in 10%, 7.5% or 5% DMSO. The study groups did not differ with regard to the diagnosis (mainly lymphomas and multiple myeloma), age, conditioning regimen, and the number of transplanted hematopoietic stem cells. 143 patients were treated with autoPBSCT. The frequency of adverse effects during and shortly after infusion was the lowest in 5% DMSO arm (p = 0.02 compared to 10% DMSO). 4 patients died due to infection before the engraftment. The median time to leukocyte and neutrophil recovery was 10 days in all study groups (p = 0.36 and p = 0.2). As well, the median day of platelet recovery was the same for all DMSO concentrations and equaled 15 days (p = 0.61).

In view of these results, 5% DMSO mixture may be considered a new standard in cryopreservation of hematopoietic stem cells.

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

Similar content being viewed by others

References

  1. Best BP. Cryoprotectant toxicity: facts, issues, and questions. Rejuvenation Res. 2015;18:422–36.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Donmez A, Tombuloglu M, Gungor A, Soyer N, Saydam G, Cagirgan S. Clinical side effects during peripheral blood progenitor cell infusion. Transfus Apher Sci. 2007;36:95–101.

    Article  PubMed  Google Scholar 

  3. Pamphilon D, Mijovic A. Storage of hemopoietic stem cells. Asian J Transfus Sci. 2007;1:71–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Shu Z, Heimfeld S, Gao D. Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion. Bone Marrow Transplant. 2014;49:469–76.

    Article  CAS  PubMed  Google Scholar 

  5. Windrum P, Morris TC, Drake MB, Niederwieser D, Ruutu T, EBMT Chronic Leukaemia Working Party Complications Subcommittee. Variation in dimethyl sulfoxide use in stem cell transplantation: a survey of EBMT centres. Bone Marrow Transplant. 2005;36:601–3.

    Article  CAS  PubMed  Google Scholar 

  6. Morris C, de Wreede L, Scholten M, Brand R, van Biezen A, Sureda A, et al. Should the standard dimethyl sulfoxide concentration be reduced? Results of a European Group for Blood and Marrow Transplantation prospective noninterventional study on usage and side effects of dimethyl sulfoxide. Transfusion. 2014;54:2514–22.

    Article  CAS  PubMed  Google Scholar 

  7. Syme R, Bewick M, Stewart D, Porter K, Chadderton T, Glück S. The role of depletion of dimethyl sulfoxide before autografting: on hematologic recovery, side effects, and toxicity. Biol Blood Marrow Transplant. 2004;10:135–41.

    Article  CAS  PubMed  Google Scholar 

  8. Akkök CA, Holte MR, Tangen JM, Ostenstad B, Bruserud O. Hematopoietic engraftment of dimethyl sulfoxide-depleted autologous peripheral blood progenitor cells. Transfusion. 2009;49:354–61.

    Article  PubMed  Google Scholar 

  9. Lecchi L, Giovanelli S, Gagliardi B, Pezzali I, Ratti I, Marconi M. An update on methods for cryopreservation and thawing of hemopoietic stem cells. Transfus Apher Sci. 2016;54:324–36.

    Article  PubMed  Google Scholar 

  10. Alencar S, Garnica M, Luiz RR, Nogueira CM, Borojevic R, Maiolino A, et al. Cryopreservation of peripheral blood stem cell: the influence of cell concentration on cellular and hematopoietic recovery. Transfusion. 2010;50:2402–12.

    Article  PubMed  Google Scholar 

  11. Akkök CA, Liseth K, Nesthus I, Løkeland T, Tefre K, Bruserud O, et al. Autologous peripheral blood progenitor cells cryopreserved with 5 and 10 percent dimethyl sulfoxide alone give comparable hematopoietic reconstitution after transplantation. Transfusion. 2008;48:877–83.

    Article  PubMed  Google Scholar 

  12. Mitrus I, Smagur A, Giebel S, Gliwinska J, Prokop M, Glowala-Kosinska M, et al. A faster reconstitution of hematopoiesis after autologous transplantation of hematopoietic cells cryopreserved in 7.5% dimethyl sulfoxide if compared to 10% dimethyl sulfoxide containing medium. Cryobiology. 2013;67:327–31.

    Article  CAS  PubMed  Google Scholar 

  13. Giebel S, Kruzel T, Czerw T, Sadus-Wojciechowska M, Najda J, Chmielowska E, et al. Intermediate-dose Ara-C plus G-CSF for stem cell mobilization in patients with lymphoid malignancies, including predicted poor mobilizers. Bone Marrow Transplant. 2013;48:915–21.

    Article  CAS  PubMed  Google Scholar 

  14. Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I. The ISHAGE guidelines for CD34+ cell determination by flow cytometry. International Society of Hematotherapy and Graft Engineering. J Hematother. 1996;5:213–26.

    Article  CAS  PubMed  Google Scholar 

  15. Smagur A, Mitrus I, Giebel S, Sadus-Wojciechowska M, Najda J, Kruzel, et al. Impact of different dimethyl sulphoxide concentrations on cell recovery, viability and clonogenic potential of cryopreserved peripheral blood hematopoietic stem and progenitor cells. Vox Sang. 2013;104:240–7.

    Article  CAS  PubMed  Google Scholar 

  16. Berz D, McCormack EM, Winer ES, Colvin GA, Quesenberry PJ. Cryopreservation of hematopoietic stem cells. Am J Hematol. 2007;82:463–72.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Rosskopf K, Ragg SJ, Worel N, Grommé M, Preijers FW, Braakman E, et al. Quality controls of cryopreserved haematopoietic progenitor cells (peripheral blood, cord blood, bone marrow). Vox Sang. 2011;101:255–75.

    Article  CAS  PubMed  Google Scholar 

  18. Bakken AM, Bruserud O, Abrahamsen JF. No differences in colony formation of peripheral blood stem cells frozen with 5 or 10% dimethyl sulfoxide. J Hematother Stem Cell Res. 2003;12:351–8.

    Article  CAS  PubMed  Google Scholar 

  19. Lanza F, Campioni DC, Hellmann A, Milone G, Wahlin A, Walewski J, et al. Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation. Biol Blood Marrow Transplant. 2013;19:1670–6.

    Article  PubMed  Google Scholar 

  20. Cox MA, Kastrup J, Hrubiško M. Historical perspectives and the future of adverse reactions associated with haemopoietic stem cells cryopreserved with dimethyl sulfoxide. Cell Tissue Bank. 2012;13:203–15.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Iwona Mitrus.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mitrus, I., Smagur, A., Fidyk, W. et al. Reduction of DMSO concentration in cryopreservation mixture from 10% to 7.5% and 5% has no impact on engraftment after autologous peripheral blood stem cell transplantation: results of a prospective, randomized study. Bone Marrow Transplant 53, 274–280 (2018). https://doi.org/10.1038/s41409-017-0056-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41409-017-0056-6

This article is cited by

Search

Quick links