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

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:62

Enthalten in:

Transfusion - 62(2022), 1 vom: 01. Jan., Seite 165-172

Sprache:

Englisch

Beteiligte Personen:

Diana, Jean-Sébastien [VerfasserIn]
Manceau, Sandra [VerfasserIn]
Leblanc, Thierry [VerfasserIn]
Magnani, Alessandra [VerfasserIn]
Magrin, Elisa [VerfasserIn]
Bendavid, Matthieu [VerfasserIn]
Couzin, Chloe [VerfasserIn]
Joseph, Laure [VerfasserIn]
Soulier, Jean [VerfasserIn]
Cavazzana, Marina [VerfasserIn]
Lefrère, Francois [VerfasserIn]

Links:

Volltext

Themen:

143011-72-7
Antigens, CD34
Cellular therapy
Clinical Trial, Phase I
Clinical Trial, Phase II
Granulocyte Colony-Stimulating Factor
Heterocyclic Compounds
Journal Article
Research Support, Non-U.S. Gov't
Therapeutic apheresis
Transplantation - stem cell

Anmerkungen:

Date Completed 12.04.2022

Date Revised 31.05.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1111/trf.16721

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM332899543