Despite numerous reports on the procoagulant activities of G-CSF, the effect of plerixafor on the hemostatic system is not clearly understood. This study aims to evaluate the effects of plerixafor on the hemostatic system when used for autologous stem cell mobilization (ASCM) for poor mobilizers (PM) with lymphoma and multiple myeloma. Patients who were performed ASCM with plerixafor in combination with GCSF were prospectively enrolled. Cohort A included patients mobilized with G-CSF whereas Cohort B included patients mobilized with G-CSF + plerixafor. Blood samples were obtained before the mobilization regimen and just before apheresis. CBC, coagulation tests, CRP, protein C and S, vWF antigen, and factors VIII and XII were studied. Cohort A (n= 30) of which 9 received chemotherapy + G-CSF. Factor VIII, INR, vWF antigen, and CRP significantly increased after G-CSF compared to baseline. Decreases in protein C and S were significant (p<0.001; p=0.005). In cohort B (n=15) no significant changes were observed in coagulation parameters Factor levels, protein C and S before and after the plerixafor. Fibrinogen decreased slightly after plerixafor administration (4.2773±2.2125 vs. 3.6987±1.5062; p=0.02). remained unchanged. In conclusion the addition of plerixafor to G-CSF did not exert further significant procoagulant effects.

Human granulocyte colony-stimulating factor (G-CSF) is a granulopoietic growth factor used in the treatment of neutropenia following chemotherapy, myeloablative treatment, or healthy donors preparing for allogeneic transplantation. Few hypersensitivity reactions (HRs) have been reported, and its true prevalence is unknown. We aimed to systematically characterize G-CSF-induced HRs while including a comprehensive list of adverse reactions. We reviewed articles published before January 2024 by searching in the PubMed, Embase, Cochrane Library, and Web of Science databases using a combination of the keywords listed, selected the ones needed, and extracted relevant data. The search resulted in 68 entries, 17 relevant to our study and 7 others found from manually searching bibliographic sources. A total of 40 cases of G-CSF-induced HR were described and classified as immediate (29) or delayed (11). Immediate ones were mostly caused by filgrastim (13 minimum), with at least 9 being grade 5 on the WAO anaphylaxis scale. Delayed reactions were mostly maculopapular exanthemas and allowed for the continuation of G-CSF. Reactions after first exposure frequently appeared and were present in at least 11 of the 40 cases. Only five desensitization protocols have been found concerning the topic at hand in the analyzed data. We believe this study brings to light the research interest in this topic that could benefit from further exploration, and propose regular updating to include the most recently published evidence.

Drugs that promote angiogenesis include statins, recombinant human granulocyte colony-stimulating factor, and stromal cell-derived factor-1. Low doses of atorvastatin could significantly increase the vascular expressions of endothelial growth factor, and the number of peripheral blood endothelial progenitor cells (EPCs), thus improving angiogenesis and local blood flow. G-CSF is an EPC-mobilization agent used in ischemia studies for targeting angiogenesis after cerebral ischemia via EPCs. In previous clinical trials, consistent conclusions have not been reached about the effectiveness of G-CSF on ischemic stroke. Therefore, the therapeutic effect of G-CSF and its combination with other medicines need further experimental verification. It is known that atorvastatin, rhG-CSF, and SDF-1 are considered the most promising neuroprotective candidates, but a comprehensive comparison of their effects is lacking.

To compare the effects of atorvastatin, stromal cell-derived factor-1, and recombinant human granulocyte colony-stimulating factor on ischemic stroke.

Adult male Sprague-Dawley rats were randomly allocated to three groups: normal, sham-operated, and middle cerebral artery occlusion operated. Middle cerebral artery occlusion operated rats were further allocated into saline, atorvastatin, recombinant human granulocyte colony-stimulating factor, and recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 groups. Neurological function evaluation, cerebral infarction and the blood-brain barrier integrity analysis, identification of angiogenic factors, assessment of angiogenesis, expression of growth-associated protein-43, neuroglobin, glial cell-derived neurotrophic factor, and cleaved caspase 3, were performed.

Compared with atorvastatin or recombinant human granulocyte colony-stimulating factor alone, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 treatment improved neurological performance, reduced cerebral infarction and blood-brain barrier disruption after stroke, and increased the content of stromal cell-derived factor-1, vascular endothelial growth factor, monocyte chemotactic protein 1, and basic fibroblast growth factor in peripheral blood. In addition, recombinant human granulocyte colony-stimulating factor + stromal cell-derived factor-1 promoted greater angiogenesis than atorvastatin or recombinant human granulocyte colony-stimulating factor alone and increased the expression of growth-associated protein-43, neuroglobin, and glial cell-derived neurotrophic factor, while decreasing the levels of cleaved caspase 3 in the brain after ischemic stroke.

Combination therapy with recombinant human granulocyte colony-stimulating factor and stromal cell-derived factor-1 is more effective than atorvastatin or recombinant human granulocyte colony-stimulating factor alone in protecting against stroke-induced damage and could be an optimal therapeutic strategy for stroke.

The potential application for stem cell therapy is vast, and development for use in ischaemic stroke is still in its infancy. Access to stem cells for research is contentious; however, stem cells are obtainable from both animal and human. Despite a limited understanding of their mechanisms of action, clinical trials assessing stem cells in human stroke have been performed. Trials are also underway evaluating haematopoietic precursors mobilised with granulocyte-colony stimulating factor, an approach offering an autologous means of administrating stem cells for therapeutic purposes. This review summarises current knowledge in regard to stem cells and their potential for helping improve recovery after stroke.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed.

In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. Granulocyte colony-stimulating factor receptors were identified in a variety of nonmyeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for peripheral blood progenitor cells, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare.

rhG-CSF effects in healthy volunteers, although normally transient and self-limiting, are now believed to be more complex and heterogeneous than previously thought. Although rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is widely used in healthy donors for collection of peripheral blood progenitor cells (PBPCs) for allogeneic transplantation and granulocytes for transfusion. The spectrum of its biologic and molecular activities in healthy individuals is coming into sharper focus, creating a unique set of challenges and clarifying the need to monitor and safeguard donor safety. Accumulating evidence indicates that rhG-CSF effects are not limited to the myeloid cell lineage. This may reflect the presence of functional G-CSF receptors on other cell types and tissues, as well as rhG-CSF-induced modulation of cytokine networks. While most rhG-CSF-induced effects are transient and self-limiting, preliminary, provocative data have suggested the possibility of a more durable effect on the chromosomal integrity of lymphocytes. While these reports have not been validated and have been subject to criticism, they are prompting prospective studies and monitoring efforts to determine whether there is a significant risk of long-term adverse events (eg, hematologic malignancies) in healthy PBPC and granulocyte donors. Based on the totality of information that is currently available, the administration of rhG-CSF to healthy donors for the purpose of PBPC donation continues to have a favorable risk-benefit profile.

Loss of motor function is common after stroke and leads to significant chronic disability. Stem cells are capable of self-renewal and of differentiating into multiple cell types, including neurones, glia, and vascular cells. We assessed the safety of granulocyte-colony-stimulating factor (G-CSF) after stroke and its effect on circulating CD34+ stem cells.

We performed a 2-center, dose-escalation, double-blind, randomized, placebo-controlled pilot trial (ISRCTN 16784092) of G-CSF (6 blocks of 1 to 10 microg/kg SC, 1 or 5 daily doses) in 36 patients with recent ischemic stroke. Circulating CD34+ stem cells were measured by flow cytometry; blood counts and measures of safety and functional outcome were also monitored. All measures were made blinded to treatment.

Thirty-six patients, whose mean+/-SD age was 76+/-8 years and of whom 50% were male, were recruited. G-CSF (5 days of 10 microg/kg) increased CD34+ count in a dose-dependent manner, from 2.5 to 37.7 at day 5 (area under curve, P=0.005). A dose-dependent rise in white cell count (P<0.001) was also seen. There was no difference between treatment groups in the number of patients with serious adverse events: G-CSF, 7/24 (29%) versus placebo 3/12 (25%), or in their dependence (modified Rankin Scale, median 4, interquartile range, 3 to 5) at 90 days.

G-CSF is effective at mobilizing bone marrow CD34+ stem cells in patients with recent ischemic stroke. Administration is feasible and appears to be safe and well tolerated. The fate of mobilized cells and their effect on functional outcome remain to be determined.

Allogeneic peripheral blood progenitor cell (PBPC) transplantation requires granulocyte-colony-stimulating factor (G-CSF) administration to mobilize PBPCs in healthy donors. The effects of G-CSF on pulmonary functions, however, have not been clearly elucidated in PBPC donors.

Respiratory status by measurements of arterial blood gas was prospectively evaluated serially in 25 healthy donors (9 men, 16 women; age, 18-61 years) administered a dose of 10 microg per kg for 5 days.

White blood cell (WBC) counts increased in all the subjects after G-CSF administration; means on Days 0, 3, and 5 were 6 x 10(9), 33.4 x 10(9), and 33.6 x 10(9) per L, respectively. The mean PaO(2) values on the respective days were 93.1, 85.8, and 81.8 mmHg, and these changes were significant (p < 0.0001), remaining significant after adjustment for the WBC count. Levels of both PaCO(2) and AaDO(2) were significantly higher after G-CSF administration than those before G-CSF administration (p < 0.0001 and p = 0.0004, respectively). SaO(2) was significantly decreased after G-CSF administration (p = 0.0002). Age was identified as a significant predictive factor for the increase of AaDO(2) and PaO(2) decline. These observations clearly indicate that the gas exchange was significantly affected during G-CSF administration in healthy PBPC donors.

Considering an increasing use of PBPC mobilization by G-CSF, careful monitoring of the respiratory status is important to ensure safety of PBPC donors, especially elderly donors.

Since their discovery just under a century ago, growth factors (GFs) have been used almost ubiquitously in haematology. Many haematological cancers are associated with bone marrow failure, either as a direct consequence of the disease or its treatment. Colony stimulating factors (CSFs) have been used to address the problems associated with the resulting cytopenias, however, concerns about the potential leukaemogenic effects of some of these CSFs led to a degree of initial hesitancy in usage, particularly in the management of acute myeloid leukaemia (AML). This has now been largely overcome. Other limitations have included cost and side effect profiles (the latter particularly with the multilineage factors). There has been wide variation locally, nationally and internationally in the usage of GFs. The American Society of Clinical Oncologists (ASCO) attempted to rationalise the usage of GFs by producing a consensus document enumerating the evidence-based indications for use of GFs. There is little information on cost effectiveness, this remains an important issue for the future. Peripheral blood stem cell transplantation (PBSCT) has revolutionised the management of many malignant conditions and has contributed to the increased use of growth factors. Many other indications are emerging for GFs used singly or in combination. Current clinical applications of GFs include: i) amelioration of cytopenias following chemotherapy and stem cell transplantation, ii) chemotherapy dose maintenance and escalation, iii) chemosensitisation and modification of disease states, iv) optimisation of methods for mobilisation of progenitor stem cells, v) immunotherapy, and vi) as therapeutic targets for treatment of haematolgical malignancies.

Granulocyte colony stimulating factor (G-CSF)-mobilized peripheral blood stem cells (PBSC) are now widely used instead of bone marrow for autologous transplantation due to earlier hematopoietic recovery after transplant. The low toxicity of G-CSF has prompted phase I and II studies to evaluate PBSC for allogeneic transplantation; these studies have demonstrated that engraftment of neutrophils, red blood cells and platelets is faster with peripheral blood cells compared to marrow. In randomized studies comparing mobilized PBSC and marrow for allogeneic transplantation, most trials have confirmed significantly earlier engraftment with PBSC and similar risks of acute graft-vs.-host disease (GVHD). In some trials, an increase of 10-15% in grade II-IV GVHD has been noted with PBSC. All studies showed a trend towards more chronic GVHD with PBSC. Some randomized studies have shown improved survival and disease-free survival with the use of PBSC due to lowered transplant-related mortality and fewer relapses in recipients of PBSC as a result of improved immune reconstitution and a graft-vs.-leukemia (GVL) effect. This survival benefit is most apparent in patients with more advanced hematologic malignancies, but further studies are needed to define the relative benefits of PBSC for patients with less advanced disease. The GVL effect of PBSC is currently being exploited with the use of non-ablative allografts.

Granulocyte colony-stimulating factor (G-CSF), which is widely used to mobilize peripheral blood stem cells (PBSC) from normal donors, has led to the use of PBSC as a major alternative to bone marrow for patients undergoing allogeneic transplants. Safety issues related to the administration of G-CSF to normal donors, however, are still under study. The short-term effects after G-CSF administration are well known and manageable. G-CSF induces a hypercoagulable state, which may predispose certain donors to thrombotic complications. A dose of 10 microg/kg/d for 5 days has been recommended for routine clinical use, but the optimal dose and schedule for PBSC collection are still being defined. Small studies to date have shown no late effects of G-CSF administration but there is insufficient information regarding any long-term adverse effects or risks. Although the administration of G-CSF to normal donors for PBSC collection appears safe, longer follow-up is required.

The harvesting of peripheral blood progenitor cells (PBPCs) after granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor stimulation instead of bone marrow in healthy donors has become increasingly popular. Donors, given the choice between bone marrow and PBPC donation, often prefer cytapheresis because of the easier access, no necessity for general anesthesia, and no multiple bone marrow punctures. In addition, accelerated engraftment and immunomodulation by granulocyte colony-stimulating factor-mobilized PBPCs are advantageous for the recipient. However, because of donor inconvenience and poor mobilization, there is a need to develop improved procedures. Aspects such as durability of hematopoietic engraftment, characterization of the earliest stem cell, and composition of PBPCs are not yet well defined, and international donor registration and follow-up must be considered when evaluating long-term safety profiles in healthy donors. This review concentrates on the most significant developments on mobilization of PBPCs published during the past year.