Rapid mobilization of functional donor hematopoietic cells without G-CSF using AMD3100, an antagonist of the CXCR4/SDF-1 interaction

Abstract

Allografts from HLA-matched sibling donors were mobilized and collected without granulocyte colony-stimulating factor (G-CSF) using AMD3100, a direct antagonist of CXCR4/stromal-derived factor 1 (SDF-1/CXCL12). Donors (N ‫؍‬ 25) were treated with AMD3100 at a dose of 240 g/kg by subcutaneous injection, and leukapheresis was then initiated just 4 hours later. Two-thirds of the donors collected an allograft with a CD34 ؉ cell dose sufficient for transplantation after just one dose of AMD3100.No donor experienced more than grade 1 toxicity. After a myeloablative regimen, 20 patients with hematologic malignancies received allografts collected after AMD3100 alone. All patients engrafted neutrophils (median day 10) and platelets (median day 12) promptly.

Mobilized peripheral blood grafts include more than hematopoietic stem cells: the immunological perspective

“…These findings might represent an immune background for the unexpected results of a phase II study by Devine et al, 64 in which 25 patients received PBSC from HLA-identical sibling donors mobilized with a single dose of plerixafor as the only agent; patients were compared with a historical group who received standard G-CSF mobilized product. The authors observed a higher content of T CD3 + and T CD4 + cells in plerixafor-mobilized grafts, with no apparent polarization toward a particular lymphocyte subset.…”

Importance of blood graft characteristics in auto-SCT: implications for optimizing mobilization regimens

“…In the study by Fruehauf et al, 88 expression of genes for chemokine receptor 4 (CXCR4), anti-apoptosis, cell cycle promotion, cell adhesion and cell motility were higher in collections after G-CSF plus plerixafor mobilization when compared with the collections after G-CSF mobilization alone. No data are available on gene expression of CD34 þ cells in patients mobilized with CT þ G-CSF þ plerixafor.…”

Ancestim (r-metHuSCF) plus filgrastim and/or chemotherapy for mobilization of blood progenitors in 513 poorly mobilizing cancer patients: the French compassionate experience

“…29 Recently, drugs targeting the CXCR-4/CXCL12 axis showed interesting results. Plerixafor has been tested in several clinical studies, which demonstrated its efficacy on progenitor cell collection when used upfront in combination with G-CSF in healthy volunteers 30,31 or in patients with lymphoid malignancies. [32][33][34][35] In addition, several studies reported the use of plerixafor in poorly mobilizing patients, with a success rate ranging from 66 to 85% in small-to medium-sized patient groups.…”