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.

  • Technical Report
  • Published:

Technical Reports

A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide vs dimethylsulfoxide with hydroxyethylstarch

Summary:

Hematopoietic stem cells intended for autologous transplantation are usually cryopreserved in solutions containing 10% dimethylsulfoxide (DMSO, v/v) or 5% DMSO in combination with 6% hydroxyethylstarch (HES, w/v). We performed a single-blinded, randomized study comparing these cryoprotectant solutions for patients undergoing autologous peripheral blood stem cell (PBSC) transplantation. A total of 294 patients were evaluable; 148 received cells frozen with 10% DMSO and 146 received cells frozen in 5% DMSO/6% HES. Patients who received cells frozen with the combination cryoprotectant recovered their white blood cell count 1.0 × 109/l at a median of 10 days, one day faster than those who received PBSC frozen with DMSO alone (P=0.04). Time to achieve neutrophil counts of 0.5 × 109 and 1.0 × 109/l were similarly faster for the recipients of the cells frozen in the combination solution. This effect was more pronounced for patients who received quantities of CD34+ cells higher than the median for the population. Median time to discontinuation of antibiotic use was also one day faster for the recipients of cells cryopreserved with DMSO/HES (P=0.04). In contrast, median times to recovery of platelet count 20 × 109/l were equivalent for each group (10 days; P=0.99) and the median numbers of red cell and platelet transfusions did not differ.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1

Similar content being viewed by others

References

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

    CAS  PubMed  Google Scholar 

  2. Areman EM, Sacher RA, Deeg HJ . Processing and storage of human bone marrow: a survey of current practices in North America. Bone Marrow Transplant 1990; 6: 203–209.

    CAS  PubMed  Google Scholar 

  3. Elliot C, McCarthy D . A survey of methods of processing and storage of bone marrow and blood stem cells in the EBMT. Bone Marrow Transplant 1994; 14: 419–423.

    Google Scholar 

  4. Karow AM, Webb WR . Tissue freezing. A theory for injury and survival. Cryobiology 1965; 2: 99–108.

    Article  PubMed  Google Scholar 

  5. Takahashi T, Hirsh A, Erbe E, Williams RJ . Mechanism of cryoprotection by extracellular polymeric solutes. Biophys J 1988; 54: 509–518.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ashwood-Smith MJ, Warby C, Connor KW, Becker G . Low-temperature preservation of mammalian cells in tissue culture with polyvinylpyrrolidone (PVP), dextrans, and hydroxyethyl starch (HES). Cryobiology 1972; 9: 441–449.

    Article  CAS  PubMed  Google Scholar 

  7. van Putten LM . Monkey and mouse bone marrow preservation and the choice of technique for human application. Proceedings of the 11th Congress International Society of Blood Transfusion, Sidney, 1968, 797–801.

  8. Stiff PJ, Murgo AJ, Zaroulis CG et al. Unfractionated human marrow cell cryopreservation using dimethylsulfoxide and hydroxyethyl starch. Cryobiology 1983; 20: 17–24.

    Article  CAS  PubMed  Google Scholar 

  9. Stiff PJ, Koester AR, Weidner MK et al. Autologous bone marrow transplantation using unfractionated cells cryopreserved in dimethylsulfoxide and hydroxyethyl starch without controlled-rate freezing. Blood 1987; 70: 974–978.

    CAS  PubMed  Google Scholar 

  10. Makino S, Harada M, Akashi K et al. A simplified method for cryopreservation of peripheral blood stem cells at −80°C without rate-controlled freezing. Bone Marrow Transplant 1991; 8: 239–244.

    CAS  PubMed  Google Scholar 

  11. Takaue Y, Abe T, Kawano Y et al. Comparative analysis of engraftment after cryopreservation of peripheral blood stem cell autografts by controlled- versus uncontrolled-rate methods. Bone Marrow Transplant 1994; 13: 801–804.

    CAS  PubMed  Google Scholar 

  12. Yu J, Leisenring W, Rowley SD et al. The predictive value of white cell or CD34+ cell count in peripheral blood for timing apheresis and maximizing yield. Transfusion 1999; 39: 442–450.

    Article  CAS  PubMed  Google Scholar 

  13. Rowley SD, Yu J, Gooley T et al. Trafficking of CD34+ cells into the peripheral circulation during collection of peripheral blood stem cells by apheresis. Bone Marrow Transplant 2001; 28: 649–656.

    Article  CAS  PubMed  Google Scholar 

  14. Rowley SD, Bensinger WI, Gooley TA, Buckner CD . Effect of cell concentration on bone marrow and peripheral blood stem cell cryopreservation. Blood 1994; 83: 2731–2736.

    CAS  PubMed  Google Scholar 

  15. Rowley SD, Byrne DV . Low-temperature storage of bone marrow in nitrogen vapor-phase refrigerators: decreased temperature gradients with an aluminum racking system. Transfusion 1992; 32: 750–754.

    Article  CAS  PubMed  Google Scholar 

  16. Bensinger WI, Schiffman KS, Holmberg L et al. High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer. Bone Marrow Transplant 1997; 19: 1183–1189.

    Article  CAS  PubMed  Google Scholar 

  17. Brunvand MW, Bensinger WI, Soll E et al. High-dose fractionated total-body irradiation, etoposide and cyclophosphamide for treatment of malignant lymphoma: comparison of autologous bone marrow and peripheral blood stem cells. Bone Marrow Transplant 1996; 18: 131–141.

    CAS  PubMed  Google Scholar 

  18. Press OW, Eary JF, Gooley T et al. A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas. Blood 2000; 96: 2934–2942.

    CAS  PubMed  Google Scholar 

  19. Bensinger WI, Appelbaum FR, Rowley S et al. Factors that influence collection and engraftment of autologous peripheral-blood stem cells. J Clin Oncol 1995; 13: 2547–2555.

    Article  CAS  PubMed  Google Scholar 

  20. Rowley SD, MacLeod B, Heimfeld S et al. Severe central nervous system toxicity associated with the infusion of cryopreserved PBSC components. Cytotherapy 1999; 1: 311–317.

    CAS  PubMed  Google Scholar 

  21. Van Putten LM . The effectiveness of different freeze storage techniques for mouse-bone-marrow cell-suspensions. Ann NY Acad Sci 1964; 114: 695–700.

    Article  PubMed  Google Scholar 

  22. Gilmore MJML . GCT-conditioned medium: an unsuitable stimulus for monitoring granulocyte–macrophage colony-forming cells in cryopreserved bone marrow. Cryobiology 1983; 20: 106–110.

    Article  CAS  PubMed  Google Scholar 

  23. Rowley SD, Hattenburg C . Cryopreservation of hematopoietic progenitor cells. Exp Hematol 1990; 18: 678 (Abstract).

    Google Scholar 

  24. Polge C, Smith AU, Parkes AS . Revival of spermatozoa after vitrification and dehydration at low temperatures. Nature 1949; 164: 666.

    Article  CAS  PubMed  Google Scholar 

  25. Lovelock JE, Bishop MWH . Prevention of freezing damage to living cells by dimethylsulphoxide. Nature 1959; 183: 1394–1395.

    Article  CAS  PubMed  Google Scholar 

  26. Galmes A, Besalduch J, Bargay J et al. Cryopreservation of hematopoietic progenitor cells with 5-percent dimethyl sulfoxide at −80 degrees C without rate-controlled freezing. Transfusion 1996; 36: 794–797.

    Article  CAS  PubMed  Google Scholar 

  27. Ragab AH, Gilkerson E, Myers M . Factors in the cryopreservation of bone marrow cells from children with acute lymphocytic leukemia. Cryobiology 1977; 14: 125–134.

    Article  CAS  PubMed  Google Scholar 

  28. Donaldson C, Armitage WJ, Denning-Kendall PA, Nicol AJ, Bradley BA, Howes JM . Optimal cryopreservation of human umbilical cord blood. Bone Marrow Transplant 1996; 18: 725–731.

    CAS  PubMed  Google Scholar 

  29. Leibo SP, Farrant J, Mazur P et al. Effects of freezing on marrow stem cell suspensions: interactions of cooling and warming rates in the presence of PVP, sucrose or glycerol. Cryobiology 1970; 6: 315–332.

    Article  CAS  PubMed  Google Scholar 

  30. Clark J, Pati A, McCarthy D . Successful cryopreservation of human bone marrow does not require a controlled-rate freezer. Bone Marrow Transplant 1991; 7: 121–125.

    CAS  PubMed  Google Scholar 

  31. Rowley SD . Techniques of bone marrow and stem cell cryopreservation and storage. In: Sacher R, AuBuchon J (eds). Marrow Transplantation: Practical and Technical Aspects of Stem Cell Reconstitution. American Association of Blood Banks: Bethesda, 1992, pp 105–127.

    Google Scholar 

  32. Bensinger W, Singer J, Appelbaum FR et al. Autologous transplantation with peripheral blood mononuclear cells collected after administration of recombinant granulocyte stimulating factor. Blood 1993; 81: 3158–3163.

    CAS  PubMed  Google Scholar 

  33. McQuaker IG, Hunter AE, Pacey S et al. Low-dose filgrastim significantly enhances neutrophil recovery following autologous peripheral-blood stem-cell transplantation in patients with lymphoproliferative disorders: evidence for clinical and economic benefit. J Clin Oncol 1997; 15: 451–457.

    Article  CAS  PubMed  Google Scholar 

  34. Davis JM, Rowley SD, Braine HG, Piantadosi S, Santos GW . Clinical toxicity of cryopreserved bone marrow graft infusion. Blood 1990; 75: 781–786.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Funding for this project was provided in part by Grants number CA18029 and CA15704 from the National Cancer Institute, Bethesda, MD, and the Jose Carreras Foundation Against Leukemia.

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rowley, S., Feng, Z., Chen, L. et al. A randomized phase III clinical trial of autologous blood stem cell transplantation comparing cryopreservation using dimethylsulfoxide vs dimethylsulfoxide with hydroxyethylstarch. Bone Marrow Transplant 31, 1043–1051 (2003). https://doi.org/10.1038/sj.bmt.1704030

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.bmt.1704030

Keywords

This article is cited by

Search

Quick links