Explore the vast range of titles available.

Purpose The aim of this project was to review the literature and define clinical practice guidelines for the use of cytokines and growth factor agents for the prevention or treatment of oral mucositis induced by cancer chemotherapy or radiotherapy. Methods A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO). The body of evidence for each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: Recommendation, Suggestion, No guideline possible. Results Sixty-four clinical studies across 11 interventions were evaluated. A recommendation was made for the use of recombinant human KGF-1 (palifermin) at a dose of 60 μg/kg per day for 3 days prior to conditioning treatment and for 3 days post-transplant for prevention of oral mucositis in patients receiving high-dose chemotherapy and total body irradiation followed by autologous stem cell transplantation for hematological malignancies. A suggestion was made against using granulocyte macrophage colony-stimulating factor mouthwash for the prevention of oral mucositis in the setting of high-dose chemotherapy followed by autologous or allogeneic stem cell transplantation. No guideline was possible for any other cytokine or growth factor agents due to inconclusive evidence. Conclusions Of the cytokine and growth factor agents studied for oral mucositis, the evidence only supports use of palifermin in the specific population listed above. Additional well-designed research is needed on other cytokine and growth factor interventions and in other cancer treatment settings.

Obtaining hematopoietic stem cells (HSCs) for transplantation depends on effective egress of HSCs from bone marrow into the peripheral circulation on induction. This process is impaired in a mouse model of diabetes and in patients undergoing autologous transplantation. Hematopoietic stem-cell (HSC) transplantation remains the primary curative treatment for patients with a variety of hematologic cancers. Transplantation of either autologous or allogeneic stem cells requires the acquisition of sufficient numbers of HSCs to ensure rapid and consistent trilineage engraftment, thus minimizing extended periods of pancytopenia after transplantation. Methods to optimize peripheralization of HSCs boost the number of HSCs that can be obtained for transplantation. These methods are based on the use of either cytokines alone (granulocyte colony-stimulating factor [G-CSF] or granulocyte–macrophage colony-stimulating factor [GM-CSF]) or cytokines plus chemotherapy to induce effective egress of HSCs from the bone marrow into . . .

In patients with autoimmune pulmonary alveolar proteinosis, the use of inhaled recombinant granulocyte–macrophage colony-stimulating factor resulted in a significantly better alveolar–arterial oxygen gradient at 25 weeks than the use of placebo. The beneficial effect was not observed in smokers.

Therapeutics against coronavirus disease 2019 (COVID-19) are urgently needed. Granulocyte–macrophage colony-stimulating factor (GM-CSF), a myelopoietic growth factor and pro-inflammatory cytokine, plays a critical role in alveolar macrophage homeostasis, lung inflammation and immunological disease. Both administration and inhibition of GM-CSF are currently being therapeutically tested in COVID-19 clinical trials. This Perspective discusses the pleiotropic biology of GM-CSF and the scientific merits behind these contrasting approaches.Recombinant granulocyte–macrophage colony-stimulating factor (GM-CSF) as well as antibodies targeted at GM-CSF or its receptor are being tested in clinical trials for coronavirus disease 2019 (COVID-19). This Perspective introduces the pleiotropic functions of GM-CSF and explores the rationale behind these different approaches.

Poorly immunogenic tumors, including triple negative breast cancers (TNBCs), remain resistant to current immunotherapies, due in part to the difficulty of reprogramming the highly immunosuppressive tumor microenvironment (TME). Here we show that peritumorally injected, macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) for concentrating dendritic cells (DCs), CpG oligonucleotides, and a doxorubicin-iRGD conjugate enhance the immunogenic death of tumor cells, increase systemic tumor-specific CD8 + T cells, repolarize tumor-associated macrophages towards an inflammatory M1-like phenotype, and significantly improve antitumor efficacy against poorly immunogenic TNBCs. This system also prevents tumor recurrence after surgical resection and results in 100% metastasis-free survival upon re-challenge. This chemo-immunotherapy that concentrates DCs to present endogenous tumor antigens generated in situ may broadly serve as a facile platform to modulate the suppressive TME, and enable in situ personalized cancer vaccination. The immunosuppressive tumour microenvironment impairs immunotherapy in poorly immunogenic cancer. Here, the authors load an alginate gel with GM-CSF, CpG oligonucleotides and doxorubicin-iRGD to promote immunogenic death of tumour cells and improve immunotherapy efficacy in triple negative breast cancer models.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34 + hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 10 6 CD34 + cells kg –1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P  < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P  < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34 + HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529 The phase 3 GENESIS trial reports the superiority of the novel CXCR4 inhibitor motixafortide with G-CSF in mobilizing hematopoietic progenitor cells for autologous stem cell transplantation in multiple myeloma.

The innate immune system represents the initial arm of host defense against pathogenic bacteria, fungi, and parasites. Neutrophils, monocytes, and tissue-based macrophages are major cellular components of this system. The potential ability to augment activity of the innate immune system has increased dramatically during the past 2 decades, with the discovery and development of cytokines. Four cytokines, namely granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interferon (IFN)-γ, have received increasing attention as potential adjunctive agents for the treatment of infectious diseases. In various animal models of infection, therapeutic administration of each of the 4 cytokines has been shown to enhance pathogen eradication and to decrease morbidity and/or mortality. However, variable therapeutic efficacy has been reported in clinical trials conducted to date. This review summarizes the current status of the use of G-CSF, GM-CSF, M-CSF, and IFN-γ in the treatment of infectious diseases.

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that is primarily secreted by monocytes or macrophages and has traditionally been recognized for its role in stimulating the proliferation and differentiation of neutrophils. Recent research has revealed the presence of G-CSF in non-hematopoietic cells such as vascular endothelial cells, placental cells, and trophoblast cells. This discovery has led to the belief that G-CSF plays a significant role in ensuring the success of pregnancy. In this review, we investigate and summarize the mechanisms of G-CSF in the reproductive system, specifically addressing its roles in endometrial repair at the maternal-fetal interface, trophoblast development, suppression of autoimmunity, ovulation, and its therapeutic effects in reproductive-related diseases. As an important cytokine in normal pregnancy, our study demonstrate that G-CSF could improve endometrial receptivity through multiple mechanisms: not only by inhibiting apoptosis, regulating cytokine expression, and mobilizing cells, but also by increasing the number of endometrial pinopodes and attenuating degeneration, as supported by recent studies. Our aim is to provide a comprehensive reference for future scientific research and clinical treatment endeavors.

Background The pharmacoeconomics of the myeloid growth factors (MGFs) is an important topic that has received substantial attention in recent years. The use of the MGFs as primary prophylaxis to prevent febrile neutropenia (FN) has grown considerably over the past decade and professional guidelines regarding their use have broadened the settings in which these agents are indicated. Recent data also suggest a potential role for them in reducing infection-related and all-cause mortality. The cost and effectiveness of these agents will continue to gain visibility as companies pursue approval for bio-similar agents in the US, similar to their recent approval in Europe. Objectives The objective of this paper is to review the available pharmaco-economic literature on the MGFs, which is particularly timely in light of the recent passage of healthcare reform and the increasing focus on cost control. The cost of treating cancer in the US is rising faster than the already rapid increase in overall medical expenditure. The clinical utility and cost effectiveness of supportive care measures in oncology must therefore be weighed carefully. This review focuses on the use of different formulations of MGFs for primary and secondary prophylaxis of chemotherapy-induced neutropenia. Methods A MEDLINE search was performed to find studies that became available since the prior review of this topic was published in Pharmacoeconomics in 2003. Results Acceptable cost-minimization estimates for primary prophylaxis with the MGFs in patients receiving cancer chemotherapy have been provided by several studies in the US. Of the commonly used agents in the US, pegfilgrastim appears to be superior to the currently recommended dose and schedule of filgrastim in terms of cost minimization, and primary prophylaxis appears to be less costly than secondary prophylaxis. However, the cost benefits of primary prophylaxis in Europe are not as pronounced as in the US, due to the lower costs of medical care. Data continue to emerge suggesting a decreased risk of early mortality from averted infections as well as the possibility of a disease-specific mortality benefit through maintaining the relative dose intensity of chemotherapy with MGF support. Conclusion This evidence will prove valuable in assessing the overall cost effectiveness and cost utility of the MGFs in patients receiving cancer chemotherapy.

To study the efficacy and safety of Polyethylene glycolated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in the prevention of neutropenia during concurrent chemoradiotherapy for nasopharyngeal carcinoma (NPC). This is a single-center, prospective, randomized controlled study conducted from June 1, 2021, to October 31, 2022 on patients diagnosed with locally advanced NPC. Participants were divided into an experimental group and a control group. The experimental group received PEG-rhG-CSF injections post-chemotherapy cycles, whereas the control group received standard care without additional intervention. Outcomes assessed included grade 3/4 neutropenia incidence, blood cell count changes, febrile neutropenia rates, delays or interruptions in chemotherapy/radiotherapy due to hematological toxicity, oral mucositis incidents, and bone pain occurrences, comparing these between both groups. 1. 88 patients with locally advanced NPC were included, the incidence of grade 3 neutropenia in the experimental group was lower than that in the control group (P = 0.026); 2. The white blood cell count and neutrophil count in D7, D10, D14, and D21 in the experimental group were higher than those in the control group (P<0.01); 3. The rate of delayed chemotherapy in the experimental group was lower than that in the control group (2.3% vs. 29.5%), P = 0.001; the rate of interruption of radiotherapy in the experimental group was lower than that in the control group (2.3% vs.27.3%), P = 0.003; 4. The incidence of bone pain in the experimental group was 34.1%, of which most were mild bone pain, and no severe bone pain occurred. The leukocyte and neutrophil counts of the patients in the bone pain group were significantly higher than those of the patients in the no bone pain group, P(WBC) = 0.001, P(ANC) = 0.002. The preventive use of PEG-rhG-CSF decreases the incidence of neutropenia in patients undergoing concurrent chemoradiotherapy for NPC, thereby reducing rates of chemotherapy delays and radiotherapy interruptions, with mild adverse reactions that are tolerable by patients.