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Preclinical evaluation of an automated closed fluid management device: CytomateTM, for washing out DMSO from hematopoietic stem cell grafts after thawing

Summary:

Infusion of dimethylsulfoxide (DMSO) contained in cryopreserved and thawed hematopoietic stem cell (HSC) grafts is frequently associated with mild or moderate adverse reactions, and occasionally with more severe events including neurological symptoms. The severity of these complications is related to the amount of residual DMSO. We evaluated a recently available, closed, automated and ‘cgmp (current good manufacturing practice) compliant’ device (CytoMateTM) for its ability to wash out DMSO at the expense of a limited loss of viable CD34+ cells. A total of 16 procedures were carried out with 39 blood HSC bags intended for destruction. Mean amounts of DMSO for each cellular product (one, two or three bags) were between 12.2 and 39.6 g before thawing; after the washing procedure, residual DMSO quantities were between 0.1 and 3.7 g. When set up to reproducibly allow for a more than 96% elimination of DMSO, processing of thawed cells with the CytoMateTM cell processor resulted in a mean recovery of viable total cells, CD34+ cells and lymphocyte subsets above 60%. We conclude that this simple and efficient washing technique is suitable for routine processing of HSC grafts. Clinical studies will demonstrate whether a reduction in the incidence of adverse effects associated with DMSO infusion is observed.

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Acknowledgements

This work was supported in part by Institut Paoli-Calmettes. We thank the technical staff of the Cell and Gene Therapy Facility (Centre de Thérapie Cellulaire et Génique) for the excellent laboratory expertise in the processing of grafts and in flow cytometry analyses. This work has been presented in part at the Eigth Annual Meeting of the International Society for Cell Therapy (ISCT).

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Calmels, B., Houzé, P., Hengesse, JC. et al. Preclinical evaluation of an automated closed fluid management device: CytomateTM, for washing out DMSO from hematopoietic stem cell grafts after thawing. Bone Marrow Transplant 31, 823–828 (2003). https://doi.org/10.1038/sj.bmt.1703905

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