Differences in Cellular Composition of Peripheral Blood Stem Cell Grafts from Healthy Stem Cell Donors Mobilized with Either Granulocyte Colony-Stimulating Factor (G-CSF) Alone or G-CSF and Plerixafor

Abstract

This study was conducted to characterize and compare peripheral blood stem cell grafts from healthy donors who underwent granulocyte colony-stimulating factor (G-CSF) mobilization and subsequently received 1 dose of plerixafor after insufficient stem cell yields were achieved at the first apheresis. Aliquots from 35 donors were collected from the first apheresis after mobilization with G-CSF alone and from the second apheresis after additional plerixafor administration. Samples were freshly analyzed for cellular subsets by 8-color flow cytometry. Leukapheresis samples mobilized with additional plerixafor showed a significant increase of total nucleated cells, including B cells, CD4 and CD8 T cells, and CD34 hematopoietic stem and progenitor cells. Absolute numbers of plasmacytoid dendritic cells were also significantly increased, whereas no changes were detected for myeloid dendritic cells. Furthermore, absolute numbers of regulatory T cells increased, with naive CD45RA regulatory T cells showing the highest rise. Finally, strikingly higher numbers of myeloid-derived suppressor cells were detected in the plerixafor and G-CSF-mobilized graft. The mobilization of peripheral stem cells in healthy donors with G-CSF and plerixafor led to a significant difference in cellular graft composition compared with G-CSF alone. The clinical impact of the different cell composition for the graft recipient warrants further clinical investigation.

Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study

“…CD34+ cells from bone marrow and mobilised peripheral blood have similar capacity to re-establish long-term haemopoiesis after allogeneic HSPC transplantation, but the use of mobilised peripheral blood is associated with a reduction in time to engraftment, probably attributable to differences in composition of progenitor cells 33 . Studies in a larger cohort of patients are needed to establish if ex-vivo gene-corrected CD34+ cells from mobilised peripheral blood and bone marrow differ in their biological properties and capacity to restore haemopoiesis after gene therapy for Wiskott-Aldrich syndrome.…”

Plerixafor combined with standard regimens for hematopoietic stem cell mobilization in pediatric patients with solid tumors eligible for autologous transplants: two-arm phase I/II study (MOZAIC)

“…a All were common terminology criteria for adverse events grade 1. patients with non-Hodgkin's lymphoma and MM [15,16]. It is known that there are differences in the cellular composition of apheresis products recovered from healthy adults who received either plerixafor plus G-CSF or G-CSF alone [17]. Nevertheless, there is no evidence from studies in adult lymphoma or MM patients that potential differences in apheresis product affects platelet engraftment [15,16].…”

“…However, in another study in children with malignant tumors, the median time to platelet engraftment with plerixafor was 16 days (range 9–30 days) [ 13 ], which is similar to the median time of 18–21 days for platelet engraftment observed for both plerixafor plus G-CSF and the G-CSF alone arms in adult patients with non-Hodgkin’s lymphoma and MM [ 15 , 16 ]. It is known that there are differences in the cellular composition of apheresis products recovered from healthy adults who received either plerixafor plus G-CSF or G-CSF alone [ 17 ]. Nevertheless, there is no evidence from studies in adult lymphoma or MM patients that potential differences in apheresis product affects platelet engraftment [ 15 , 16 ].…”

Potentially modifiable predictors of cell collection efficiencies and product characteristics of allogeneic hematopoietic progenitor cell collections

“…Due to target cell loss with CD34+ selection of 30%–50% 1 and subsequent manufacturing steps, high numbers of CD34+ cells are targeted for collection. Lymphocytes or monocytes for immune effector cell therapy may also be sourced from previously collected HPC products 2 and may be enriched in desirable characteristics, such as lower risk of causing graft versus host disease 3,4 . Thus, collection procedure strategies to improve collection efficiency (CE) and, thus, yield of desired peripheral blood (PB) target cell types would be helpful.…”