Granulocyte–colony stimulating factor plus plerixafor inpatients with –thalassemia major results in the effective mobilization of primitiveCD34+ cells with specific gene expression profile

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Abstract

Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic stem and progenitor cells (HSPCs) with high repopulating capacity. Previous studies suggested superior mobilization in these patients by the combination of granulocyte–colony stimulating factor (G-CSF) plus plerixafor over single agents. We mobilized four adult patients using G-CSF+plerixafor to assess the intra-individual variation of the circulating CD34+ cells number and subtypes preand post-plerixafor administration. The procedure was well-tolerated and the target cell dose of ≥8.106 CD34+ cells/kg was achieved in three of them with one apheresis procedure. The addition of plerixafor unanimously increased the number of circulating CD34+ cells, and the frequency of the most primitive CD34+ subtypes: CD34+/38- and CD34+/133+/38- as well as the in vitro clonogenic potency. Microarray analyses of CD34+ cells purified from the leukapheresis of one patient mobilized twice, with G-CSF and with G-CSF+plerixafor, highlighted in G-CSF+plerixafor-mobilized CD34+ cells, higher levels of expression genes involved in HSPC motility, homing, and cell cycles. In conclusion, G-CSF+plerixafor in β-thalassemia patients mobilizes optimal numbers of HSPCs with characteristics that suggest high capacity of engraftment after transplantation.
Lingua originaleEnglish
pagine (da-a)11-17
Numero di pagine7
RivistaThalassemia Reports
Volume7
Stato di pubblicazionePublished - 2017

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beta-Thalassemia
Transcriptome
Hematopoietic Stem Cells
Inpatients
Thalassemia
Tissue Array Analysis
Leukapheresis
Blood Component Removal
JM 3100
Genetic Therapy
Cell Movement
Cell Cycle
Cell Count
Transplantation
Gene Expression
Genes

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title = "Granulocyte–colony stimulating factor plus plerixafor inpatients with –thalassemia major results in the effective mobilization of primitiveCD34+ cells with specific gene expression profile",
abstract = "Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic stem and progenitor cells (HSPCs) with high repopulating capacity. Previous studies suggested superior mobilization in these patients by the combination of granulocyte–colony stimulating factor (G-CSF) plus plerixafor over single agents. We mobilized four adult patients using G-CSF+plerixafor to assess the intra-individual variation of the circulating CD34+ cells number and subtypes preand post-plerixafor administration. The procedure was well-tolerated and the target cell dose of ≥8.106 CD34+ cells/kg was achieved in three of them with one apheresis procedure. The addition of plerixafor unanimously increased the number of circulating CD34+ cells, and the frequency of the most primitive CD34+ subtypes: CD34+/38- and CD34+/133+/38- as well as the in vitro clonogenic potency. Microarray analyses of CD34+ cells purified from the leukapheresis of one patient mobilized twice, with G-CSF and with G-CSF+plerixafor, highlighted in G-CSF+plerixafor-mobilized CD34+ cells, higher levels of expression genes involved in HSPC motility, homing, and cell cycles. In conclusion, G-CSF+plerixafor in β-thalassemia patients mobilizes optimal numbers of HSPCs with characteristics that suggest high capacity of engraftment after transplantation.",
keywords = "CD34+ cells expression profiling, G-CSF+plerixafor mobilization, gene therapy, β-thalassemia",
author = "Flavia Contino and Salvatore Feo",
year = "2017",
language = "English",
volume = "7",
pages = "11--17",
journal = "Thalassemia Reports",
issn = "2039-4365",
publisher = "PagePress Publications",

}

TY - JOUR

T1 - Granulocyte–colony stimulating factor plus plerixafor inpatients with –thalassemia major results in the effective mobilization of primitiveCD34+ cells with specific gene expression profile

AU - Contino, Flavia

AU - Feo, Salvatore

PY - 2017

Y1 - 2017

N2 - Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic stem and progenitor cells (HSPCs) with high repopulating capacity. Previous studies suggested superior mobilization in these patients by the combination of granulocyte–colony stimulating factor (G-CSF) plus plerixafor over single agents. We mobilized four adult patients using G-CSF+plerixafor to assess the intra-individual variation of the circulating CD34+ cells number and subtypes preand post-plerixafor administration. The procedure was well-tolerated and the target cell dose of ≥8.106 CD34+ cells/kg was achieved in three of them with one apheresis procedure. The addition of plerixafor unanimously increased the number of circulating CD34+ cells, and the frequency of the most primitive CD34+ subtypes: CD34+/38- and CD34+/133+/38- as well as the in vitro clonogenic potency. Microarray analyses of CD34+ cells purified from the leukapheresis of one patient mobilized twice, with G-CSF and with G-CSF+plerixafor, highlighted in G-CSF+plerixafor-mobilized CD34+ cells, higher levels of expression genes involved in HSPC motility, homing, and cell cycles. In conclusion, G-CSF+plerixafor in β-thalassemia patients mobilizes optimal numbers of HSPCs with characteristics that suggest high capacity of engraftment after transplantation.

AB - Successful gene therapy for β-thalassemia requires optimal numbers of autologous gene-transduced hematopoietic stem and progenitor cells (HSPCs) with high repopulating capacity. Previous studies suggested superior mobilization in these patients by the combination of granulocyte–colony stimulating factor (G-CSF) plus plerixafor over single agents. We mobilized four adult patients using G-CSF+plerixafor to assess the intra-individual variation of the circulating CD34+ cells number and subtypes preand post-plerixafor administration. The procedure was well-tolerated and the target cell dose of ≥8.106 CD34+ cells/kg was achieved in three of them with one apheresis procedure. The addition of plerixafor unanimously increased the number of circulating CD34+ cells, and the frequency of the most primitive CD34+ subtypes: CD34+/38- and CD34+/133+/38- as well as the in vitro clonogenic potency. Microarray analyses of CD34+ cells purified from the leukapheresis of one patient mobilized twice, with G-CSF and with G-CSF+plerixafor, highlighted in G-CSF+plerixafor-mobilized CD34+ cells, higher levels of expression genes involved in HSPC motility, homing, and cell cycles. In conclusion, G-CSF+plerixafor in β-thalassemia patients mobilizes optimal numbers of HSPCs with characteristics that suggest high capacity of engraftment after transplantation.

KW - CD34+ cells expression profiling

KW - G-CSF+plerixafor mobilization

KW - gene therapy

KW - β-thalassemia

UR - http://hdl.handle.net/10447/236558

UR - http://www.pagepressjournals.org/index.php/thal/

M3 - Article

VL - 7

SP - 11

EP - 17

JO - Thalassemia Reports

JF - Thalassemia Reports

SN - 2039-4365

ER -