Background: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-alpha beta/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition.Methods: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 'poor mobilizers' (PM) failing to attain = 40 CD34(+) HSCs/L after 4 daily G-CSF doses and/or with predicted apheresis yields = 12.0x106 CD34(+) cells/kg recipient's body weight.Results: MZ significantly increased CD34(+) counts in PM. Na ve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16(+) monocytes and the down-regulation of IFN-gamma production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs.Conclusions: MZ facilitates the collection of mega-doses of CD34(+) HSCs for haploidentical HSCT, while affecting graft composition.

Rutella, S., Filippini, P., Bertaina, V., Li Pira, G., Altomare, L., Ceccarelli, S., Brescia, L. P., Lucarelli, B., Girolami, E., Conflitti, G., Cefalo, M. G., Bertaina, A., Corsetti, T., Moretta, L., Locatelli, F., Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts, <<JOURNAL OF TRANSLATIONAL MEDICINE>>, 2014; 12 (1): 1-14. [doi:10.1186/s12967-014-0240-z] [https://hdl.handle.net/10807/242054]

Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts

Locatelli, Franco
2014

Abstract

Background: HLA-haploidentical hematopoietic stem cell transplantation (HSCT) is suitable for patients lacking related or unrelated HLA-matched donors. Herein, we investigated whether plerixafor (MZ), as an adjunct to G-CSF, facilitated the collection of mega-doses of hematopoietic stem cells (HSC) for TCR-alpha beta/CD19-depleted haploidentical HSCT, and how this agent affects the cellular graft composition.Methods: Ninety healthy donors were evaluated. Single-dose MZ was given to 30 'poor mobilizers' (PM) failing to attain = 40 CD34(+) HSCs/L after 4 daily G-CSF doses and/or with predicted apheresis yields = 12.0x106 CD34(+) cells/kg recipient's body weight.Results: MZ significantly increased CD34(+) counts in PM. Na ve/memory T and B cells, as well as natural killer (NK) cells, myeloid/plasmacytoid dendritic cells (DCs), were unchanged compared with baseline. MZ did not further promote the G-CSF-induced mobilization of CD16(+) monocytes and the down-regulation of IFN-gamma production by T cells. HSC grafts harvested after G-CSF + MZ were enriched in myeloid and plasmacytoid DCs, but contained low numbers of pro-inflammatory 6-sulfo-LacNAc+ (Slan)-DCs. Finally, children transplanted with G-CSF + MZ-mobilized grafts received greater numbers of monocytes, myeloid and plasmacytoid DCs, but lower numbers of NK cells, NK-like T cells and Slan-DCs.Conclusions: MZ facilitates the collection of mega-doses of CD34(+) HSCs for haploidentical HSCT, while affecting graft composition.
2014
Inglese
Rutella, S., Filippini, P., Bertaina, V., Li Pira, G., Altomare, L., Ceccarelli, S., Brescia, L. P., Lucarelli, B., Girolami, E., Conflitti, G., Cefalo, M. G., Bertaina, A., Corsetti, T., Moretta, L., Locatelli, F., Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts, <<JOURNAL OF TRANSLATIONAL MEDICINE>>, 2014; 12 (1): 1-14. [doi:10.1186/s12967-014-0240-z] [https://hdl.handle.net/10807/242054]
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