Immunobiology of allogeneic peripheral blood mononuclear cells mobilized with granulocyte-colony stimulating factor

Abstract

Summary:The use of mobilized peripheral blood (PB) stem cells for autologous transplantation initially generated much enthusiasm because of enhanced engraftment in comparison to marrow stem cells and avoidance of general anesthesia for the donor. Its application to the allogeneic setting seemed inevitable. For obvious ethical reasons, allogeneic donors are mobilized with cytokines only, mainly granulocyte colony-stimulating factor (G-CSF).Results from preliminary studies suggest that in comparison to standard bone marrow transplants, outcomes such as engraftment, host-versus-graft reaction, graftversus-host disease, graft-versus-leukemia and immunological reconstitution may be different. Surprisingly, G-CSF, previously recognized as a late acting lineage-specific factor for neutrophil production, not only disrupts homeostasis between stem cells and their microenvironment, but also induces significant quantitative and qualitative changes in the accessory cell compartment, affecting lymphocytes, monocytes, natural killer, dendritic, and stromal cells. Furthermore, mobilization of huge numbers of non-professional antigen presenting cells (CD34 + stem cells) amplifies the tolerizing potential of PB stem cell grafts. Thus, G-CSF mobilization provides PB transplants with different immunobiologic properties in comparison to standard bone marrow grafts. Whether these immunobiologic differences will lead to better transplant outcomes remains to be shown through much awaited results of large randomized clinical trials. Bone Marrow Transplantation (2000) 26, 1-16. Keywords: stem cells; transplantation; mobilization; microenvironment; alloreactivity; polarization Since the first reported case of allogeneic peripheral blood mononuclear cell (PBMNC) transplantation, 1 PBMNCs mobilized with granulocyte colony-stimulating factor (GPBMNCs) are being increasingly used as a source

rhG-CSF does not affect the phenotype of adult donor peripheral blood NK cells

“…[19][20][21][22][23]25 While results vary between studies, the influence of rhG-CSF has been reported on monocytes, 21 T cells [21][22][23] and NK cells. 20,22,23 There are contradictory reports on changes in the absolute numbers of NK cells and their proportion within total lymphocytes, following rhG-CSF administration.…”

“…18 In this context, it is important to determine what are the consequences on lymphocyte populations of the use of pharmacological doses of rhG-CSF to mobilise haematopoietic progenitors in donors. Most published reports [19][20][21][22][23][24] have focused on T-cell phenotype or function, and suggest that rhG-CSF may truly be an immunomodulator in addition to being a mobilisation agent. Manipulation of the NK cell compartment will require an assessment of the consequences of rhG-CSF exposure on this cell population.…”

Hepatitis B virus reactivation with clinical flare in allogeneic stem cell transplants with chronic graft-versus-host disease

“…Awareness of the association between HBV reactivation and cGVHD is especially relevant when one considers that cGVHD occurs in the majority of patients receiving HLA non-identical-related transplants, matched unrelated transplants, and HLA matched mobilized peripheral blood allogeneic stem cell transplants. 44,45 As suggested by Strasser and McDonald, 46 these patients should be monitored for HBV DNA from 2 weeks post transplant. Early initiation of pre-emptive antiviral therapy upon obtaining positive results may abrogate HBV replication during the window of post-transplant defective thymopoiesis and limit CTL-induced hepatocellular damage at the critical time of immune recovery and immunosuppressive therapy withdrawal.…”

CD137 Induces Proliferation of Murine Hematopoietic Progenitor Cells and Differentiation to Macrophages

“…G-CSF is being used to reconstitute the hematopoietic system of cancer patients after chemotherapy or radiation therapy, whereas erythropoietin and thrombopoietin are being used for the treatment of anemia and thrombocytopenia, respectively (4,5).…”