title: Mobilization of healthy donors with plerixafor affects the cellular composition of T-cell receptor (TCR)-αβ/CD19-depleted haploidentical stem cell grafts.
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.
authors.affiliation: Department of Pediatric Hematology/Oncology and Transfusion Medicine, IRCCS Bambino Gesù Children's Hospital, Rome, Italy. sergio.rutella@gmail.com.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Perla
authors.initials: P
authors.lastname: Filippini
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaina
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Li Pira
authors.forename: Lidia
authors.initials: L
authors.lastname: Altomare
authors.forename: Stefano
authors.initials: S
authors.lastname: Ceccarelli
authors.forename: Letizia P
authors.initials: LP
authors.lastname: Brescia
authors.forename: Barbarella
authors.initials: B
authors.lastname: Lucarelli
authors.forename: Elia
authors.initials: E
authors.lastname: Girolami
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Conflitti
authors.forename: Maria Giuseppina
authors.initials: MG
authors.lastname: Cefalo
authors.forename: Alice
authors.initials: A
authors.lastname: Bertaina
authors.forename: Tiziana
authors.initials: T
authors.lastname: Corsetti
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D064591:Allografts; D018941:Antigens, CD19 / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001596:Benzylamines; D001788:Blood Grouping and Crossmatching; D002452:Cell Count; D002648:Child; D000080027:Cyclams; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006402:Hematologic Diseases / Q000276:immunology / Q000628:therapy*; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D006801:Humans; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D014019:Tissue Donors
chemical_list: D018941:Antigens, CD19; D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor