The use of AMD3100 plus G-CSF for autologous hematopoietic progenitor cell mobilization is superior to G-CSF alone

Abstract

Hematopoietic progenitor cells (HPCs) traffic to and are retained in the marrow through the trophic effects of the chemokine stromal cell-derived factor-1␣ (SDF-1␣) binding to its receptor, CXC chemokine receptor 4 (CXCR4). AMD3100 reversibly inhibits SDF-1␣/CXCR4 binding, and AMD3100 administration mobilizes CD34 ؉ cells into the circulation. We therefore tested the hypotheses that the combination of AMD3100 plus granulocyte colony-stimulating factor (G- CSF

Improving stem cell mobilization strategies: future directions

“…[136][137][138] Plerixafor used in conjunction with G-CSF has been shown in a phase 2 study to quickly and predictably enhance the numbers of CD34 þ cells circulating in the peripheral blood. 139 In this study, patients with NHL mobilized more CD34 þ cells per day of apheresis after administration of plerixafor plus G-CSF than after administration of G-CSF alone (median increase of 4.4-fold (range: 1.1-to 54.4-fold)). Similar results were seen in patients with MM (median increase of 3-to 3.5-fold (range: 1.3-to 10-fold)).…”

“…139 In patients in whom mobilization with G-CSF either alone or in combination with chemotherapy has previously failed, CD34 þ cell yields have been noted to increase by 5-to 100-fold in response to administration of plerixafor plus G-CSF. 139,140 A cohort of 115 patients termed poor mobilizers who received plerixafor as part of a compassionate use protocol was assessed by Calandra et al 140 Collections of X2 Â 10 6 CD34 þ cells/kg after administration of plerixafor plus G-CSF for mobilization were achieved in 60.3% of patients with NHL, 71.4% of patients with MM and 76.5% of patients with HD; these rates were similar for patients who had previously failed mobilization with chemotherapy plus cytokines or cytokines alone. 140 Preliminary results of two phase 3 multicenter randomized placebo-controlled studies indicated that the addition of plerixafor to a G-CSF regimen resulted in greater efficacy than was seen with a regimen of G-CSF alone.…”

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

“…25 These effects resemble those of AML cell stimulation by G-CSF or GM-CSF, and synergy between the activities of hematopoietic growth factors (at least G-CSF) and CXCR4 inhibitors has been reported. [27][28][29] A mechanism of action for the beneficial effect of priming with GM-CSF could, therefore, be mediated through CXCR4-induced mobilization. CXCR4 expression in AML is correlated with FLT3 gene mutation, 23 and CXCR4 inhibition increased the sensitivity of FLT3-mutated leukemic cells to the apoptogenic effects of FLT3 inhibitors.…”

Rescue from failed growth factor and/or chemotherapy HSC mobilization with G-CSF and plerixafor (AMD3100): an institutional experience

“…16,17 Plerixafor has been shown to rapidly increase circulating CD34 þ progenitor cells in preclinical murine models and healthy volunteers alone or in combination with G-CSF. [17][18][19] Other clinical trials were performed combining plerixafor and G-CSF for multiple myeloma or non-Hodgkin's lymphoma patients in first or second complete or PR planned for auto-SCT. Significant enhancement of PBSC mobilization was shown.…”