A new step in understanding stem cell mobilization in patients with Fanconi anemia : A bridge to gene therapy
© 2021 AABB..
BACKGROUND: Fanconi anemia (FA) is an inherited disorder characterized clinically by congenital abnormalities, progressive bone marrow failure (BMF), and a predisposition to malignancy. Gene therapy (GT) of FA, via the infusion of gene-corrected peripheral blood (PB) autologous hematopoietic stem cells (HSCs), may constitute a cure for BMF. GT bypasses the donor restrictions and adverse events associated with allogenic HSC transplantation. However, adequate harvesting of PB-HSCs is a crucial determinant of successful engraftment in gene therapy. Harvesting the low numbers of HSCs in patients with FA is particularly challenging.
STUDY DESIGN AND METHODS: This open-label phase I/II trial evaluates the feasibility and safety of co-administration of G-CSF and plerixafor in patients with FA for the mobilization and harvesting of peripheral HSCs, intending to use them in a gene therapy trial. Patients with mutations in the FANCA gene received two subcutaneous injections of G-CSF (6 μg/kg × 2/d from D1 to D8. Plerixafor (0.24 mg/kg/d) was administered 2 h before apheresis (from D5 onward).
RESULTS: CD34+ cells were mobilized for four patients quickly but transiently after the plerixafor injection. One patient had a CD34+ cell count of over 100/μl; the mobilization peaked 2 h after the injection and lasted for more than 9 h. There were no short-term adverse events associated with the mobilization or harvesting procedures.
CONCLUSION: Our data in patients with FA show that the mobilization of HSCs with G-CSF and plerixafor is safe and more efficient in younger individuals without BMF.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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Enthalten in: |
Transfusion - 62(2022), 1 vom: 01. Jan., Seite 165-172 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Diana, Jean-Sébastien [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 12.04.2022 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1111/trf.16721 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM332899543 |
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100 | 1 | |a Diana, Jean-Sébastien |e verfasserin |4 aut | |
245 | 1 | 2 | |a A new step in understanding stem cell mobilization in patients with Fanconi anemia |b A bridge to gene therapy |
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520 | |a © 2021 AABB. | ||
520 | |a BACKGROUND: Fanconi anemia (FA) is an inherited disorder characterized clinically by congenital abnormalities, progressive bone marrow failure (BMF), and a predisposition to malignancy. Gene therapy (GT) of FA, via the infusion of gene-corrected peripheral blood (PB) autologous hematopoietic stem cells (HSCs), may constitute a cure for BMF. GT bypasses the donor restrictions and adverse events associated with allogenic HSC transplantation. However, adequate harvesting of PB-HSCs is a crucial determinant of successful engraftment in gene therapy. Harvesting the low numbers of HSCs in patients with FA is particularly challenging | ||
520 | |a STUDY DESIGN AND METHODS: This open-label phase I/II trial evaluates the feasibility and safety of co-administration of G-CSF and plerixafor in patients with FA for the mobilization and harvesting of peripheral HSCs, intending to use them in a gene therapy trial. Patients with mutations in the FANCA gene received two subcutaneous injections of G-CSF (6 μg/kg × 2/d from D1 to D8. Plerixafor (0.24 mg/kg/d) was administered 2 h before apheresis (from D5 onward) | ||
520 | |a RESULTS: CD34+ cells were mobilized for four patients quickly but transiently after the plerixafor injection. One patient had a CD34+ cell count of over 100/μl; the mobilization peaked 2 h after the injection and lasted for more than 9 h. There were no short-term adverse events associated with the mobilization or harvesting procedures | ||
520 | |a CONCLUSION: Our data in patients with FA show that the mobilization of HSCs with G-CSF and plerixafor is safe and more efficient in younger individuals without BMF | ||
650 | 4 | |a Clinical Trial, Phase I | |
650 | 4 | |a Clinical Trial, Phase II | |
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700 | 1 | |a Magrin, Elisa |e verfasserin |4 aut | |
700 | 1 | |a Bendavid, Matthieu |e verfasserin |4 aut | |
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700 | 1 | |a Joseph, Laure |e verfasserin |4 aut | |
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700 | 1 | |a Lefrère, Francois |e verfasserin |4 aut | |
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