The case for plerixafor to replace filgrastim as the optimal agent to mobilize peripheral blood donors for allogeneic hematopoietic cell transplantation

Abstract

Granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral blood progenitor cells (G-PBs) from either a related or unrelated donor continue to be the preferred donor source for most allogeneic hematopoietic cell transplantation (HCT). Recently, the American Society for Blood and Marrow Transplantation has recommended marrow instead of G-PBs as an unrelated graft source due to its lower rate of chronic graft-versus-host disease (cGVHD). However, the use of marrow is limited by both clinical considerations (slower rate of engraftment and increased donor morbidity) and logistical considerations (use of operating room resources and increased physician utilization), so this recommendation has not been widely adopted. An optimal donor source would include the rapid engraftment characteristic and the low donor morbidity associated with G-PBs and a rate of cGVHD similar to or lower than that of marrow. Recent data suggest that plerixafor mobilized PBs (P-PBs) have the rapid engraftment characteristics of G-PBs in allogeneic HCT with less cGVHD. The biologic mechanism of the lower rate of cGVHD appears to be through mobilization of regulator natural killer cells and plasmacytoid dendritic cell precursors that are associated with lower acute and chronic GVHD compared with G-PBs and rapid engraftment characterized by rapid myeloid-repopulating capacity. We suggest that, based on the experience of the two Phase II clinical trials and the unique biology of plerixafor-mobilized donor product, it should be evaluated in Phase III trials as an approach to replacing G-CSF mobilization for allogeneic HCT.

CXCR4 blockade reduces the severity of murine heart allograft rejection by plasmacytoid dendritic cell-mediated immune regulation

“…CXCR4 is widely expressed in the hematopoietic cell compartment 61 . Hence, application of CXCR4 antagonists does not only lead to a mobilization of hematopoietic stem and progenitor cells but is accompanied by marked leukocytosis that affects all hematopoietic lineages including T reg cells 60 , 62 . Moreover, homing into and retention of both, T reg cells 56 and DCs 63 , in the bone marrow have been proposed to be dependent on CXCR4/SDF1α interaction as well as the constitutive expression of VCAM-1 and endothelial selectins 28 .…”

Use of Plerixafor for Stem Cell Mobilization in the Setting of Autologous and Allogeneic Stem Cell Transplantations: An Update

“…Immunologic studies have shown higher CD3+ and CD4+ cell counts in grafts mobilized with plerixafor, however there was no increase in the incidence of graft-versus-host disease. 72 Some studies have shown that in allogeneic SCT engraftment of neutrophils and platelets after stem cell mobilization with plerixafor was faster than that with mobilization failure with G-CSF. 67 , 73 …”

Mobilization of Leukemic Cells Using Plerixafor as Part of a Myeloablative Preparative Regimen for Patients with Acute Myelogenous Leukemia Undergoing Allografting: Assessment of Safety and Tolerability

“…Plerixafor remains the sole CXCR4 antagonist approved by the Food and Drug Administration for this indication. Recent studies have also provided evidence that plerixafor may be an effective alternative to G-CSF mobilization of PB stem cells for healthy allogeneic donors, associated with rapid engraftment and potentially lower rates of cGVHD [21].…”