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Transplant Technology

Transportation and cryopreservation may impair haematopoietic stem cell function and engraftment of allogeneic PBSCs, but not BM

Abstract

Recent data suggest that the practice of using frozen allogeneic grafts is becoming increasingly common among transplant centres. Therefore, we retrospectively analysed 31 frozen allogeneic PBSC and 8 BM grafts by flow cytometry with regard to their CD34+ content, membrane integrity (7-AAD) and stem cell-specific enzyme activity (aldehyde dehydrogenase, ALDH) in relation to individual transplantation results. Membrane integrity of CD34+ cells was significantly impaired in cryopreserved PBSC but not in BM compared to unfrozen allografts. In 9 out of 31 frozen PBSC (but none of the BM) grafts numbers of SSCloALDHbr cells per kg body weight (BW) were significantly reduced while in the same grafts the numbers of CD34+ cells per kg BW were close to normal. Overall, 9 out of 33 patients (27%) who received unrelated PBSC allografts cryopreserved after transportation did not achieve engraftment. For comparison, primary graft failure was observed in our centre in only 7 out of 493 recipients (1.4%) of fresh allogeneic PBSC grafts. Moreover, we did not see any graft failure in patients receiving frozen/thawed BM or autologous PBSC transplants. We, therefore, conclude that PBSC grafts become much more sensitive to cryopreservation after transport and/or storage. Importantly, the engraftment potential of frozen HSC grafts may reliably be predicted by measuring ALDH activity.

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References

  1. Frey NV, Lazarus HM, Goldstein SC . 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 2006; 38: 399–405.

    Article  CAS  Google Scholar 

  2. 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 

  3. 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 

  4. Stockschläder M, Krüger W, Kroschke G, Zeller W, Hoffknecht M, Löliger C et al. Use of cryopreserved bone marrow in allogeneic bone marrow transplantation. Bone Marrow Transplant 1995; 15: 569–572.

    PubMed  Google Scholar 

  5. Stockschläder M, Krüger W, tom Dieck A, Horstmann M, Altnöder M, Löliger C et al. Use of cryopreserved bone marrow in unrelated allogeneic transplantation. Bone Marrow Transplant 1996; 17: 197–199.

    PubMed  Google Scholar 

  6. Stockschläder M, Hassan HA, Krog C, Krüger W, Löliger 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  Google Scholar 

  7. 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 

  8. Lioznov M, Ikogho R, Fehse B, Bacher U, Kröger N, Zander AR . Factors predicting haematological reconstitution following haemopoietic stem cell transplantation. Bone Marrow Transplant 2008 (in press).

  9. Lioznov M, Freiberger P, Kröger N, Zander AR, Fehse B . Aldehyde dehydrogenase activity as a marker for the quality of hematopoietic stem cell transplants. Bone Marrow Transplant 2005; 35: 909–914.

    Article  CAS  Google Scholar 

  10. Sputtek A, Sputtek R . Cryopreservation in transfusion medicine and hematology.In: Fuller BJ, Lane N, Benson EE (eds). Life in the Frozen State. CRC Press: Boca Raton, 2004, pp 483–504.

    Chapter  Google Scholar 

  11. Sputtek A, Jetter S, Hummel K, Kühnl P . Cryopreservation of peripheral blood progenitor cells: characteristics of suitable techniques. Beitr Infusionsther Transfusionsmed 1997; 34: 79–83.

    CAS  PubMed  Google Scholar 

  12. Fehse N, Fehse B, Kröger N, Zabelina T, Freiberger P, Krüger W et al. Influence of anti-thymocyte globulin as part of the conditioning regimen on immune reconstitution following matched related bone marrow transplantation. J Hematother Stem Cell Res 2003; 12: 237–242.

    Article  Google Scholar 

  13. Philpott NJ, Turner AJ, Scopes J, Westby M, Marsh JC, Gordon-Smith EC et al. The use of 7-amino actinomycin D in identifying apoptosis: simplicity of use and broad spectrum of application compared with other techniques. Blood 1996; 87: 2244–2251.

    CAS  PubMed  Google Scholar 

  14. Fehse B, Uhde A, Fehse N, Eckert HG, Clausen J, Rüger R et al. Selective immunoaffinity-based enrichment of CD34+ cells transduced with retroviral vectors containing an intracytoplasmatically truncated version of the human low-affinity nerve growth factor receptor (ΔLNGFR) gene. Human Gene Ther 1997; 8: 1815–1824.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank P Freiberger, U Fritzsche-Friedland, E Merle and M Reckhaus for the excellent technical assistance, and G Amtsfeld and J Hagelberg for their help with clinical data.

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Correspondence to A R Zander.

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Lioznov, M., Dellbrügger, C., Sputtek, A. et al. Transportation and cryopreservation may impair haematopoietic stem cell function and engraftment of allogeneic PBSCs, but not BM. Bone Marrow Transplant 42, 121–128 (2008). https://doi.org/10.1038/bmt.2008.93

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