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

• Published in: Journal of translational medicine Vol. 12; no. 1; p. 240
• Main Authors: Rutella, Sergio, Filippini, Perla, Bertaina, Valentina, Li Pira, Giuseppina, Altomare, Lidia, Ceccarelli, Stefano, Brescia, Letizia P, Lucarelli, Barbarella, Girolami, Elia, Conflitti, Gianpiero, Cefalo, Maria Giuseppina, Bertaina, Alice, Corsetti, Tiziana, Moretta, Lorenzo, Locatelli, Franco
• Format: Journal Article
• Language: English
• Published: 02.09.2014
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-014-0240-z

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 > or =40 CD34 super(+) HSCs/[mu]L after 4 daily G-CSF doses and/or with predicted apheresis yields < or =12.0x10 super(6) CD34 super(+) cells/kg recipient's body weight. Results: MZ significantly increased CD34 super(+) counts in PM. Naive/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 super(+) 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 super(+) (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 super(+) HSCs for haploidentical HSCT, while affecting graft composition.