A new step in understanding stem cell mobilization in patients with Fanconi anemia: A bridge to gene therapy

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.