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Fresh or frozen grafts for allogeneic stem cell transplantation: conceptual considerations and a survey on the practice during the COVID-19 pandemic from the EBMT Infectious Diseases Working Party (IDWP) and Cellular Therapy & Immunobiology Working Party (CTIWP) – Bone Marrow Transplantation

  • Worel N, Shaw BE, Aljurf M, Koh M, Seber A, Weisdorf D, et al. Changes in Hematopoietic Cell Transplantation Practices in Response to COVID-19: A Survey from the Worldwide Network for Blood & Marrow Transplantation. Transpl Cell Ther. 2021;27:270. https://doi.org/10.1016/j.jtct.2020.11.019.

    Article  CAS  Google Scholar 

  • Faulkner J, O’Brien WJ, McGrane B, Wadsworth D, Batten J, Askew CD, et al. Physical activity, mental health and well-being of adults during initial COVID-19 containment strategies: A multi-country cross-sectional analysis. J Sci Med Sport. 2021;24:320–6. https://doi.org/10.1016/j.jsams.2020.11.016.

    Article  PubMed  Google Scholar 

  • Al Hamed R, Bazarbachi AH, Malard F, Harousseau JL, Mohty M. Current status of autologous stem cell transplantation for multiple myeloma. Blood Cancer J. 2019;9:44. https://doi.org/10.1038/s41408-019-0205-9.

    Article  PubMed  PubMed Central  Google Scholar 

  • Mohty M, Hubel K, Kroger N, Aljurf M, Apperley J, Basak GW, et al. Autologous haematopoietic stem cell mobilisation in multiple myeloma and lymphoma patients: a position statement from the European Group for Blood and Marrow Transplantation. Bone Marrow Transplant. 2014;49:865–72. https://doi.org/10.1038/bmt.2014.39.

    Article  CAS  PubMed  Google Scholar 

  • Gunn N, Damon L, Varosy P, Navarro W, Martin T, Ries C, et al. High CD34+ cell dose promotes faster platelet recovery after autologous stem cell transplantation for acute myeloid leukemia. Biol Blood Marrow Transpl. 2003;9:643–8. https://doi.org/10.1016/s1083-8791(03)00232-5.

    Article  Google Scholar 

  • Czerw T, Labopin M, Schmid C, Cornelissen JJ, Chevallier P, Blaise D, et al. High CD3+ and CD34+ peripheral blood stem cell grafts content is associated with increased risk of graft-versus-host disease without beneficial effect on disease control after reduced-intensity conditioning allogeneic transplantation from matched unrelated donors for acute myeloid leukemia – an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Oncotarget. 2016;7:27255–66. https://doi.org/10.18632/oncotarget.8463.

    Article  PubMed  PubMed Central  Google Scholar 

  • Arcuri LJ, Nabhan SK, Cunha R, Nichele S, Ribeiro AAF, Fernandes JF, et al. Impact of CD34 Cell Dose and Conditioning Regimen on Outcomes after Haploidentical Donor Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide for Relapsed/Refractory Severe Aplastic Anemia. Biol Blood Marrow Transpl. 2020;26:2311–7. https://doi.org/10.1016/j.bbmt.2020.09.007.

    Article  CAS  Google Scholar 

  • Czerw T, Iacobelli S, Malpassuti V, Koster L, Kroger N, Robin M, et al. Impact of donor-derived CD34 + infused cell dose on outcomes of patients undergoing allo-HCT following reduced intensity regimen for myelofibrosis: a study from the Chronic Malignancies Working Party of the EBMT. Bone marrow Transplant. 2022;57:261–70. https://doi.org/10.1038/s41409-021-01540-2.

    Article  CAS  PubMed  Google Scholar 

  • Politikos I, Davis E, Nhaissi M, Wagner JE, Brunstein CG, Cohen S, et al. Guidelines for Cord Blood Unit Selection. Biol Blood Marrow Transpl. 2020;26:2190–6. https://doi.org/10.1016/j.bbmt.2020.07.030.

    Article  Google Scholar 

  • Ruggeri A. Optimizing cord blood selection. Hematol Am Soc Hematol Educ Program. 2019;2019:522–31. https://doi.org/10.1182/hematology.2019000056.

    Article  Google Scholar 

  • Blazar BR, Hill GR, Murphy WJ. Dissecting the biology of allogeneic HSCT to enhance the GvT effect whilst minimizing GvHD. Nat Rev Clin Oncol. 2020;17:475–92. https://doi.org/10.1038/s41571-020-0356-4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuball J, Boelens JJ. Clinical and Biological Concepts for Mastering Immune Reconstitution After HSCT: Toward Practical Guidelines and Greater Harmonization. In: th, Carreras E, Dufour C, Mohty M, Kroger N (eds). The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies: Cham (CH), 2019, pp 69–74.

  • Cox JH, Ferrari G, Kalams SA, Lopaczynski W, Oden N, D’Souza MP, et al. Results of an ELISPOT proficiency panel conducted in 11 laboratories participating in international human immunodeficiency virus type 1 vaccine trials. AIDS Res Hum Retroviruses. 2005;21:68–81. https://doi.org/10.1089/aid.2005.21.68.

    Article  CAS  PubMed  Google Scholar 

  • Ramachandran H, Laux J, Moldovan I, Caspell R, Lehmann PV, Subbramanian RA. Optimal thawing of cryopreserved peripheral blood mononuclear cells for use in high-throughput human immune monitoring studies. Cells. 2012;1:313–24. https://doi.org/10.3390/cells1030313.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Y, Mateu E, Diaz I. Impact of Cryopreservation on Viability, Phenotype, and Functionality of Porcine PBMC. Front Immunol. 2021;12:765667. https://doi.org/10.3389/fimmu.2021.765667.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Panch SR, Srivastava SK, Elavia N, McManus A, Liu S, Jin P, et al. Effect of Cryopreservation on Autologous Chimeric Antigen Receptor T Cell Characteristics. Mol Ther. 2019;27:1275–85. https://doi.org/10.1016/j.ymthe.2019.05.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pi CH, Hornberger K, Dosa P, Hubel A. Understanding the freezing responses of T cells and other subsets of human peripheral blood mononuclear cells using DSMO-free cryoprotectants. Cytotherapy. 2020;22:291–300. https://doi.org/10.1016/j.jcyt.2020.01.013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu H, Cao W, Huang L, Xiao M, Cao Y, Zhao L, et al. Effects of cryopreservation on chimeric antigen receptor T cell functions. Cryobiology. 2018;83:40–47. https://doi.org/10.1016/j.cryobiol.2018.06.007.

    Article  CAS  PubMed  Google Scholar 

  • Costantini A, Mancini S, Giuliodoro S, Butini L, Regnery CM, Silvestri G, et al. Effects of cryopreservation on lymphocyte immunophenotype and function. J Immunol Methods. 2003;278:145–55. https://doi.org/10.1016/s0022-1759(03)00202-3.

    Article  CAS  PubMed  Google Scholar 

  • Luo Y, Wang P, Liu H, Zhu Z, Li C, Gao Y. The state of T cells before cryopreservation: Effects on post-thaw proliferation and function. Cryobiology. 2017;79:65–70. https://doi.org/10.1016/j.cryobiol.2017.08.008.

    Article  CAS  PubMed  Google Scholar 

  • Capelle CM, Cire S, Ammerlaan W, Konstantinou M, Balling R, Betsou F, et al. Standard PBMC cryopreservation selectively decreases detection of nine clinically-relevant T-cell markers. ImmunoHorizons. 2021. https://doi.org/10.1101/2021.05.18.443634.

  • Svalgaard JD, Talkhoncheh MS, Haastrup EK, Munthe-Fog L, Clausen C, Hansen MB, et al. Pentaisomaltose, an Alternative to DMSO. Engraftment of Cryopreserved Human CD34(+) Cells in Immunodeficient NSG Mice. Cell Transpl. 2018;27:1407–12. https://doi.org/10.1177/0963689718786226.

    Article  Google Scholar 

  • Duchez P, Chevaleyre J, Brunet de la Grange P, Vlaski M, Boiron JM, Wouters G, et al. Cryopreservation of hematopoietic stem and progenitor cells amplified ex vivo from cord blood CD34+ cells. Transfusion. 2013;53:2012–9. https://doi.org/10.1111/trf.12015.

    Article  CAS  PubMed  Google Scholar 

  • Sartor M, Antonenas V, Garvin F, Webb M, Bradstock KF. Recovery of viable CD34+ cells from cryopreserved hemopoietic progenitor cell products. Bone Marrow Transpl. 2005;36:199–204. https://doi.org/10.1038/sj.bmt.1705009.

    Article  CAS  Google Scholar 

  • Berens C, Heine A, Müller J, Held SAE, Mayer K, Brossart P, et al. Variable resistance to freezing and thawing of CD34-positive stem cells and lymphocyte subpopulations in leukapheresis products. Cytotherapy. 2016;18:1325–31. https://doi.org/10.1016/j.jcyt.2016.06.014.

    Article  CAS  PubMed  Google Scholar 

  • Kaushal R, Jahan S, McGregor C, Pineault N. Dimethyl sulfoxide-free cryopreservation solutions for hematopoietic stem cell grafts. Cytotherapy. 2022;24:272–81. https://doi.org/10.1016/j.jcyt.2021.09.002.

    Article  CAS  PubMed  Google Scholar 

  • Pollock K, Yu G, Moller-Trane R, Koran M, Dosa PI, McKenna DH, et al. Combinations of Osmolytes, Including Monosaccharides, Disaccharides, and Sugar Alcohols Act in Concert During Cryopreservation to Improve Mesenchymal Stromal Cell Survival. Tissue Eng Part C Methods. 2016;22:999–1008. https://doi.org/10.1089/ten.TEC.2016.0284.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumura K, Hyon SH. Polyampholytes as low toxic efficient cryoprotective agents with antifreeze protein properties. Biomaterials. 2009;30:4842–9. https://doi.org/10.1016/j.biomaterials.2009.05.025.

    Article  CAS  PubMed  Google Scholar 

  • Ota A, Matsumura K, Lee JJ, Sumi S, Hyon SH. StemCell Keep Is Effective for Cryopreservation of Human Embryonic Stem Cells by Vitrification. Cell Transpl. 2017;26:773–87. https://doi.org/10.3727/096368916X692654.

    Article  Google Scholar 

  • Li R, Hornberger K, Dutton JR, Hubel A. Cryopreservation of Human iPS Cell Aggregates in a DMSO-Free Solution-An Optimization and Comparative Study. Front Bioeng Biotechnol. 2020;8:1. https://doi.org/10.3389/fbioe.2020.00001.

    Article  PubMed  PubMed Central  Google Scholar 

  • Pasley S, Zylberberg C, Matosevic S. Natural killer-92 cells maintain cytotoxic activity after long-term cryopreservation in novel DMSO-free media. Immunol Lett. 2017;192:35–41. https://doi.org/10.1016/j.imlet.2017.09.012.

    Article  CAS  PubMed  Google Scholar 

  • Lamure S, Paul F, Gagez AL, Delage J, Vincent L, Fegueux N, et al. A Retrospective Comparison of DLI and gDLI for Post-Transplant Treatment. J Clin Med. 2020;9. https://doi.org/10.3390/jcm9072204.

  • Lasky LC, Van Buren N, Weisdorf DJ, Filipovich A, McGlave P, Kersey JH, et al. Successful allogeneic cryopreserved marrow transplantation. Transfusion. 1989;29:182–4. https://doi.org/10.1046/j.1537-2995.1989.29289146840.x.

    Article  CAS  PubMed  Google Scholar 

  • 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 Transpl. 1993;11:125–31.

    CAS  Google Scholar 

  • 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 Transpl. 1996;17:197–9.

    CAS  Google Scholar 

  • 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;96:382–6. https://doi.org/10.1046/j.1365-2141.1997.d01-2032.x.

    Article  CAS  PubMed  Google Scholar 

  • Parody R, Caballero D, Marquez-Malaver FJ, Vazquez L, Saldana R, Madrigal MD, et al. To freeze or not to freeze peripheral blood stem cells prior to allogeneic transplantation from matched related donors. Eur J Haematol. 2013;91:448–55. https://doi.org/10.1111/ejh.12140.

    Article  PubMed  Google Scholar 

  • Kim DH, Jamal N, Saragosa R, Loach D, Wright J, Gupta V, et al. Similar outcomes of cryopreserved allogeneic peripheral stem cell transplants (PBSCT) compared to fresh allografts. Biol Blood Marrow Transpl. 2007;13:1233–43. https://doi.org/10.1016/j.bbmt.2007.07.003.

    Article  CAS  Google Scholar 

  • Alotaibi AS, Prem S, Chen S, Lipton JH, Kim DD, Viswabandya A, et al. Fresh vs. frozen allogeneic peripheral blood stem cell grafts: A successful timely option. Am J Hematol. 2021;96:179–87. https://doi.org/10.1002/ajh.26033.

  • Medd P, Nagra S, Hollyman D, Craddock C, Malladi R. Cryopreservation of allogeneic PBSC from related and unrelated donors is associated with delayed platelet engraftment but has no impact on survival. Bone marrow Transplant. 2013;48:243–8. https://doi.org/10.1038/bmt.2012.118.

    Article  CAS  PubMed  Google Scholar 

  • Dagdas S, Ucar MA, Ceran F, Gunes AK, Falay M, Ozet G. Comparison of allogenic stem cell transplantations performed with frozen or fresh stem cell products with regard to GVHD and mortality. Transfus Apher Sci. 2020;59:102742. https://doi.org/10.1016/j.transci.2020.102742.

    Article  PubMed  Google Scholar 

  • Ghobadi A, Fiala MA, Ramsingh G, Gao F, Abboud CN, Stockerl-Goldstein K, et al. Fresh or Cryopreserved CD34(+)-Selected Mobilized Peripheral Blood Stem and Progenitor Cells for the Treatment of Poor Graft Function after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transpl. 2017;23:1072–7. https://doi.org/10.1016/j.bbmt.2017.03.019.

    Article  CAS  Google Scholar 

  • Jacob RP, Flynn J, Devlin SM, Maloy M, Giralt SA, Maslak P, et al. Universal Engraftment after Allogeneic Hematopoietic Cell Transplantation Using Cryopreserved CD34-Selected Grafts. Transpl Cell Ther. 2021;27:697.e691–5. https://doi.org/10.1016/j.jtct.2021.04.026.

    Article  CAS  Google Scholar 

  • Hamadani M, Zhang MJ, Tang XY, Fei M, Brunstein C, Chhabra S, et al. Graft Cryopreservation Does Not Impact Overall Survival after Allogeneic Hematopoietic Cell Transplantation Using Post-Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis. Biol Blood Marrow Transpl. 2020;26:1312–7. https://doi.org/10.1016/j.bbmt.2020.04.001.

    Article  CAS  Google Scholar 

  • Hsu JW, Farhadfar N, Murthy H, Logan BR, Bo-Subait S, Frey N, et al. The Effect of Donor Graft Cryopreservation on Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center for International Blood and Marrow Transplant Research Analysis. Implications during the COVID-19 Pandemic. Transpl Cell Ther. 2021;27:507–16. https://doi.org/10.1016/j.jtct.2021.03.015.

    Article  CAS  Google Scholar 

  • Eapen M, Zhang MJ, Tang XY, Lee SJ, Fei MW, Wang HL, et al. Hematopoietic Cell Transplantation with Cryopreserved Grafts for Severe Aplastic Anemia. Biol Blood Marrow Transpl. 2020;26:e161–6. https://doi.org/10.1016/j.bbmt.2020.04.027.

    Article  CAS  Google Scholar 

  • Fadeyi E, Mamo YT, Saha AK, Wilson E, Pomper G. The Viability of Hematopoietic Progenitor Cell Grafts after Cryopreservation Does Not Predict Delayed Engraftment in Allogeneic Hematopoietic Stem Cell Transplantation. Lab Med. 2022;53:509–13. https://doi.org/10.1093/labmed/lmac042.

    Article  PubMed  Google Scholar 

  • Novitzky-Basso I, Remberger M, Chen C, Pasic I, Lam W, Law A, et al. Anti-thymocyte globulin and post-transplant cyclophosphamide predisposes to inferior outcome when using cryopreserved stem cell grafts. Eur J Haematol. 2022;108:61–72. https://doi.org/10.1111/ejh.13714.

    Article  CAS  PubMed  Google Scholar 

  • Maurer K, Kim HT, Kuczmarski TM, Garrity HM, Weber A, Reynolds CG, et al. Impact of cryopreservation and transit times of allogeneic grafts on hematopoietic and immune reconstitution. Blood Adv. 2021;5:5140–9. https://doi.org/10.1182/bloodadvances.2021005139.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bankova AK, Caveney J, Yao B, Ramos TL, Bogeholz J, Heydari K, et al. Real-World Experience of Cryopreserved Allogeneic Hematopoietic Grafts during the COVID-19 Pandemic: A Single-Center Report. Transpl Cell Ther. 2022;28:215.e211–e210. https://doi.org/10.1016/j.jtct.2022.01.010.

    Article  CAS  Google Scholar 

  • Guo M, Liu J, Clark P, Ahmad S, Patel R, Varela JC, et al. Cryopreserved versus fresh peripheral blood allogeneic stem cell transplantation outcomes in patients receiving post-transplant cyclophosphamide for graft-versus-host prophylaxis during the COVID-19 pandemic: a single center experience. Int J Hematol. 2022:1–10. https://doi.org/10.1007/s12185-022-03493-8.

  • Wiercinska E, Schlipfenbacher V, Bug G, Bader P, Verbeek M, Seifried E, et al. Allogeneic transplant procurement in the times of COVID-19: Quality report from the central European cryopreservation site. J Transl Med. 2021;19:145. https://doi.org/10.1186/s12967-021-02810-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nijssen K, Westinga K, Stuut A, Janssen A, van Rhenen A, van der Wagen L, et al. Graft engineering: how long can you wait, how low can you go, and pandemic readiness. Bone Marrow Transpl. 2023: 1–3. https://doi.org/10.1038/s41409-023-01976-8.

  • Facchin G, Savignano C, Battista ML, Isola M, De Martino M, Petruzzellis G, et al. Impact of Cryopreservation of Peripheral Blood Stem Cells (PBSC) in Transplantation from Matched Unrelated Donor (MUD). J Clin Med. 2022; 11. https://doi.org/10.3390/jcm11144114.

  • de Witte M, Daenen LGM, van der Wagen L, van Rhenen A, Raymakers R, Westinga K, et al. Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust. Hemasphere. 2021;5:e580. https://doi.org/10.1097/HS9.0000000000000580.

    Article  PubMed  PubMed Central  Google Scholar 

  • de Witte MA, Mooyaart JE, Hoogenboom JD, Chabannon C, Malard F, Ruggeri A, et al. Activity of ex vivo graft and DLI Engineering within the last decade increases, a survey from the EBMT Cellular Therapy & Immunobiology Working Party. Bone Marrow Transpl. 2023. https://doi.org/10.1038/s41409-023-01953-1.

  • Purtill D, Antonenas V, Chiappini P, Tong D, O’Flaherty E, Bajel A, et al. Variable CD34+ recovery of cryopreserved allogeneic HPC products: transplant implications during the COVID-19 pandemic. Blood Adv. 2020;4:4147–50. https://doi.org/10.1182/bloodadvances.2020002431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wolf J, Lee J, Pearce R, Wilson M, Snowden JA, Orchard K. The impact of COVID-19 on related-donor allogeneic stem cell harvest processes: A British Society of Blood and Marrow Transplantation and Cellular Therapy survey. Br J Haematol. 2022;198:e51–53. https://doi.org/10.1111/bjh.18299.

    Article  CAS  PubMed  Google Scholar 

  • Schmidt AH, Buk D, Bernas SN, Mengling T, Neujahr E, van den Brink MRM. A DKMS (German Bone Marrow Donor Center) view on cryopreservation of unrelated donor stem cell products during the Covid-19 pandemic. Am J Hematol. 2021;96:E91–92. https://doi.org/10.1002/ajh.26081.

    Article  CAS  PubMed  PubMed Central  Google Scholar