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

• Published in: Journal of translational medicine 2014-09, Vol.12 (1), p.240-240, Article 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: Article
• Language: English
• Subjects: Allografts; Antigens, CD19 - metabolism; Antigens, CD34 - metabolism; Blood Grouping and Crossmatching; Cell Count; Child; Granulocyte Colony-Stimulating Factor - administration & dosage; Hematologic Diseases - immunology; Hematologic Diseases - therapy; Hematopoietic Stem Cell Mobilization - methods; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - metabolism; Hematopoietic Stem Cells - physiology; Heterocyclic Compounds - administration & dosage; Humans; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Tissue Donors
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-014-0240-z

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. 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. 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. MZ facilitates the collection of mega-doses of CD34+ HSCs for haploidentical HSCT, while affecting graft composition.