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

Authors :
Maria Giuseppina Cefalo
Stefano Ceccarelli
Lorenzo Moretta
Gianpiero Conflitti
Giuseppina Li Pira
Valentina Bertaina
Barbarella Lucarelli
Perla Filippini
Sergio Rutella
Tiziana Corsetti
Alice Bertaina
Elia Girolami
Franco Locatelli
Lidia Altomare
Letizia Pomponia Brescia
Source :
Journal of Translational Medicine
Publisher :
Springer Nature

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-αβ/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/μL 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. Naïve/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-γ 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. Electronic supplementary material The online version of this article (doi:10.1186/s12967-014-0240-z) contains supplementary material, which is available to authorized users.

Details

Language :
English
ISSN :
14795876
Volume :
12
Issue :
1
Database :
OpenAIRE
Journal :
Journal of Translational Medicine
Accession number :
edsair.doi.dedup.....2dd27eb79ab16391d8ea2399d8d267e4
Full Text :
https://doi.org/10.1186/s12967-014-0240-z