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

Rutella, S. ORCID: 0000-0003-1970-7375, 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. and Locatelli, F., 2014. 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, 12 (1), p. 240. ISSN 1479-5876

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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.

Item Type: Journal article
Publication Title: Journal of Translational Medicine
Creators: 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. and Locatelli, F.
Publisher: BioMed Central Ltd.
Date: 2 September 2014
Volume: 12
Number: 1
ISSN: 1479-5876
Identifiers:
NumberType
10.1186/s12967-014-0240-zDOI
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 12 Sep 2016 13:29
Last Modified: 13 Oct 2017 13:51
URI: http://irep.ntu.ac.uk/id/eprint/28453

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