A case of resected anaplastic carcinoma of the pancreas producing granulocyte-colony stimulating factor with literature review.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF)-producing tumors have been reported in various organs, and the prognosis of patients with G-CSF-producing pancreatic cancers is particularly dismal. In this report, we present a case of G-CSF-producing anaplastic carcinoma of the pancreas (ACP), characterized by early postoperative recurrence and rapid, uncontrolled growth. CASE PRESENTATION: A 74-year-old man presented to our hospital with complaints of abdominal fullness and pain after eating. On admission, it was observed that the peripheral leukocyte counts and serum G-CSF levels were significantly elevated (23,770/µL and 251 pg/mL, respectively). Computed tomography of the abdomen revealed a pancreatic head tumor involving the superior mesenteric vein. Pathologically, ultrasound-guided fine-needle aspiration confirmed ACP. Subsequently, we performed a subtotal stomach-preserving pancreaticoduodenectomy with portal vein reconstruction and partial transverse colon resection. On postoperative day (POD) 7, the leukocyte count decreased from 21,180/µL to 8490/µL; moreover, computed tomography revealed liver metastasis. Therefore, mFOLFILINOX chemotherapy was initiated on POD 30. However, the tumor exhibited rapid progression, and the patient died on POD 45. CONCLUSIONS: G-CSF-producing ACP is rare, and the prognosis of patients is extremely poor. Basic research is required to develop effective drugs against G-CSF-producing tumors, and large-scale studies using national databases are needed to develop multidisciplinary treatment methods.

The granulocyte colony-stimulating factor produced during Streptococcus suis infection controls neutrophil recruitment in the blood without affecting bacterial clearance.

Streptococcus suis causes diseases in pigs and has emerged as a zoonotic agent. When infected, the host develops an exacerbated inflammation that can lead to septic shock and meningitis. Although neutrophils greatly infiltrate the lesions, their dynamics during S. suis infection remain poorly described. Moreover, very few studies reported on the production and role of a key factor in the regulation of neutrophils: the colony-stimulating granulocyte factor (G-CSF). In this study, we characterized the G-CSF-neutrophil axis in the pathogenesis of S. suis induced disease. Using a mouse model of S. suis infection, we first evaluated the recruitment of neutrophils and their activation profile by flow cytometry. We found that infection provokes a massive neutrophil recruitment from the bone marrow to the blood and spleen. In both compartments, neutrophils displayed multiple activation markers. In parallel, we observed high systemic levels of G-CSF, with a peak of production coinciding with that of neutrophil recruitment. We then neutralized the effects of G-CSF and highlighted its role in the release of neutrophils from the bone marrow to the blood. However, it did not affect bacteremia nor the cytokine storm induced by S. suis. In conclusion, systemic G-CSF induces the release of neutrophils from the bone marrow to the blood, but its role in inflammation or bacterial clearance seems to be compensated by unknown factors. A better understanding of the role of neutrophils and inflammatory mediators could lead to better strategies for controlling the infection caused by S. suis.

A Case of Revelation Due to Pegfilgrastim.

Pegfilgrastim is a granulocyte colony-stimulating factor used in non-myeloid cancer patients to prevent infections and neutropenic fevers. Although this medication is widely used to induce granulocytosis in pancytopenia patients, there are certain instances where such a situation can cause severe side effects. In this case, we present a patient with a history of metastatic colon cancer who is currently taking pegfilgrastim to counter the agranulocytosis caused by his chemotherapy treatment. However, the patient shortly developed localized left-sided jaw swelling, and upon further investigation, the granulocyte colony-stimulating factor revealed an underlying bacteremia. A discussion will also be held regarding the mechanism of action of how pegfilgrastim induced this patient's symptoms as well as the risks and benefits.

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch.

RESEARCH QUESTION: Despite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DESIGN: A retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. RESULTS: 79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. CONCLUSION: The use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

A retrospective study on the efficacy of pegfilgrastim-filgrastim combination regimen in the mobilization for autologous stem cell transplantation in lymphoma patients.

BACKGROUND: The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF) in autologous hematopoietic stem cell transplantation (auto-HSCT) in lymphomas is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: 107 lymphoma patients who received auto-HSCT were retrospectively enrolled and divided into groups of PEG+FIL and FIL. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 µg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 µg /kg/day depending on the number of PBSCs. RESULTS: The incidence of neutropenic fever in the group of PEG+FIL was significantly lower than in the group of FIL. The mean recovery time of leukocytes at autologous stem cell transplantation was significantly shorter in the group of PEG+FIL than in the group of FIL. Compared to the groups of FIL, the group of PEG+FIL had lower hospitalization costs. We found that the combination therapy is more recommended for patients with a bone marrow hematopoietic area of less than 30 %. Filgrastim is best administered 5-6 days after pegfilgrastim administration. CONCLUSIONS: Compared to conventional filgrastim mobilization, the combination of pegfilgrastim and filgrastim schedule has high efficacy, non-inferior safety, and superior health economic benefits during auto-HSCT.

Mecapegfilgrastim for prophylaxis of febrile neutropenia in children and adolescents with rhabdomyosarcoma or Ewing sarcoma: a prospective, single-arm, pilot study.

BACKGROUND: The chemotherapy regimens recommended for both rhabdomyosarcoma (RMS) and Ewing sarcoma (ES) patients are myelosuppressive and can reduce the absolute neutrophil count (ANC) and subsequently increase the risk of febrile neutropenia (FN). However, only a few studies have focused on the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) drugs in pediatric and adolescent patients with RMS and ES. Our objective was to investigate the efficacy and safety of mecapegfilgrastim, a biosimilar of pegfilgrastim, in prophylaxis of FN for pediatric and adolescent patients with RMS or ES. METHODS: In this single-arm, single-center, prospective study, pediatric and adolescent patients with RMS or ES were enrolled to receive either VAC (vincristine, cyclophosphamide, dactinomycin) regimen or VDC (vincristine, cyclophosphamide, doxorubicin) regimen in a 3-week cycle, followed by treatment with mecapegfilgrastim (100 µg/kg, maximum 6 mg) given at 24 h after completing chemotherapy. The primary endpoint was the incidence rate of FN. Secondary endpoints included the incidence rate of grade 4 neutropenia, duration of ANC ≤ 0.5 × 109/L, incidence rate of chemotherapy delay or reduction, use of antibiotics, and safety profile. RESULTS: In total, 2 of the 30 (6.7%, 95% CI: 0.82-22.07) patients experienced FN after the first cycle of chemotherapy. Eight (26.7%, 95% CI: 12.28-45.89) patients experienced grade 4 neutropenia after receiving prophylactic mecapegfilgrastim. Eight patients experienced ANC ≤ 0.5 × 109/L with a median duration of 4.5 days; among them, 6 patients reached the lowest point of their ANC level on day 7, and 5 of them recovered by day 10. No dose reductions, delays, or discontinuation of chemotherapy was reported. Twenty-one (70.0%) patients received antibiotics during the treatment period. No patient experienced FN in the 0-5 years and the 13-18 years groups, and 2 patients experienced FN in the 6-12 years group. Two patients, 6 patients, and no patient experienced grade 4 neutropenia in the 0-5 years, 6-12 years, and 13-18 years groups, respectively. CONCLUSION: Mecapegfilgrastim showed acceptable efficacy and safety profile in pediatric and adolescent patients with RMS or ES. Further randomized studies with large sample size are warranted. TRIAL REGISTRATION: This clinical trial was registered at Chictr.org.cn (No.ChiCTR1900022249). Registered on March 31, 2019.

Efficacy and safety of G-CSF prophylaxis in patients with extensive-stage small cell lung cancer receiving chemoimmunotherapy.

OBJECTIVES: We aimed to evaluate the efficacy and safety of granulocyte-colony stimulating factor (G-CSF) prophylaxis during chemoimmunotherapy with carboplatin plus etoposide and atezolizumab in extensive-stage small cell lung cancer (ES-SCLC). METHODS: This retrospective, multicenter study enrolled ES-SCLC patients receiving carboplatin plus etoposide and atezolizumab, categorized into G-CSF and non-G-CSF groups. Demographic and disease-related data were collected. Response rates, progression-free survival (PFS), overall survival (OS), and toxicity were analyzed. RESULTS: Of 119 patients (median age: 63 years), the overall response rate (ORR) and disease control rate (DCR) were 72.3% and 81.5%, respectively. In the G-CSF group, the ORR was 76.4% compared to 60.0% in the non-G-CSF group (p = 0.33), and the DCR was 85.4% versus 70.0%, respectively (p = 0.46). Median PFS was 8.3 months (95% CI, 6.8-9.8) in the G-CSF group and 6.8 months (95% CI, 6.2-7.5) in the non-G-CSF group (p = 0.24). Median OS was 13.8 months (95% CI, 9.6-18.1) for the G-CSF group and 10.6 months (95% CI, 7.9-13.3) for the non-G-CSF group (p = 0.47). Grade 3 ≥ adverse events were similar between groups (49.4% vs. 33.3%, respectively, p = 0.12). CONCLUSION: G-CSF prophylaxis can be safely used in ES-SCLC patients undergoing carboplatin plus etoposide and atezolizumab regimen without significantly altering efficacy or increasing toxicity.

Hematopoietic Growth Factors Regulate the Entry of Monocytes into the Adult Brain via Chemokine Receptor CCR5.

Monocytes are circulating macrophage precursors generated from bone marrow hematopoietic stem cells. In adults, monocytes continuously replenish cerebral border-associated macrophages under physiological conditions. Monocytes also rapidly infiltrate the brain in pathological settings. The mechanisms of recruiting monocyte-derived macrophages into the brain under pathological conditions have been extensively studied. However, it remains unclear how monocytes enter the brain to renew border-associated macrophages under physiological conditions. Using both in vitro and in vivo approaches, this study reveals that a combination of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF), complementarily and synergistically enhances the adhesion of monocytes to cerebral endothelial cells in a dose-dependent manner. Cysteine-cysteine chemokine receptor 5 (CCR5) in brain endothelial cells, but not the cell adhesion molecules mediating neuroinflammation-related infiltration of monocyte-derived macrophages, modulates SCF+G-CSF-enhanced monocyte-endothelial cell adhesion. Blocking CCR5 or genetically deleting CCR5 reduces monocyte-endothelial cell adhesion induced by SCF+G-CSF. The SCF+G-CSF-enhanced recruitment of bone marrow-derived monocytes/macrophages into the cerebral perivascular space is also reduced in adult CCR5 knockout mice. This study demonstrates the role of SCF and G-CSF in regulating the entry of monocytes into the adult brain to replenish perivascular macrophages.

The clinical impact of primary granulocyte-colony stimulating factor prophylaxis in children with acute lymphoblastic leukemia who underwent induction chemotherapy.

BACKGROUND: Data describing the risk factors for the occurrence of severe infections in acute lymphoblastic leukemia (ALL) patients following induction chemotherapy and the role of prophylactic granulocyte-colony stimulating factor (G-CSF) in the era of antimicrobials prophylaxis are limited. METHODS: This study enrolled 188 children aged ≤18 years with newly diagnosed ALL who received Taiwan Pediatric Oncology Group ALL-2002 and 2013 treatments between January 1, 2010 and June 30, 2021. Prophylactic G-CSF was administered when a patient continues neutropenia after achieving the first bone marrow remission since June 1, 2015. Clinical factors were assessed for their association with severe infections. RESULTS: From January 2010 to May 2015, 80 children experienced a total of 11 (13.5%) episodes of severe infections; while 10 (9.2%) episodes were reported to occur in 108 patients who received prophylactic G-CSF. Reduction of severe infections occurrence did not achieve statistical significance during prophylactic G-CSF administration in ALL patients. Compared with ALL-high risk (HR) and very high risk patients with no G-CSF prophylaxis, the use of G-CSF prophylaxis significantly reduced episodes of febrile neutropenia. Occurrence of grade III-IV intestinal ileus, grade II-III oral mucositis, prolonged neutropenia, central venous catheter (CVC) placement, or the requirement insulin therapy for hyperglycemia were associated with higher risk of bloodstream infections. CONCLUSIONS: ALL-HR patients with G-CSF prophylaxis were associated with reduction of febrile neutropenia episodes. Occurrence of severe ileus, oral mucositis, hyperglycemia, CVC placement, or prolonged neutropenia were associated with severe infections in ALL patients receiving induction chemotherapy.

Impact of PEG-GCSF in Breast Cancer Patients Undergoing Chemotherapy During the COVID-19 Pandemic: Single Center Experience and Literature Review.

BACKGROUND/AIM: The COVID-19 pandemic brought many challenges in healthcare systems globally. Pegylated granulocyte colony stimulating factor (PEG-GCSF) is recommended to reduce febrile neutropenia (FN), however there are a few reports that G-CSF might worsen COVID-19 disease, and its appropriate use during the COVID-19 pandemic remains uncertain. This retrospective study aimed to analyze the association between PEG-GCSF use and COVID-19 infection and severity. PATIENTS AND METHODS: Breast cancer patients who received chemotherapy at the Nagoya Tokushukai General Hospital between October 2020 and April 2023 were included. Patients with suspected COVID-19 symptoms during each chemotherapy cycle underwent COVID-19 antigen testing. To assess the potential impact of PEG-GCSF on COVID-19 severity, we collected data on patient background, chemotherapy regimens, PEG-GCSF use, COVID-19 antigen tests, and COVID-19 infection from their medical records. RESULTS: Thirty patients received chemotherapy. In total, 71 cycles were administered comprising adriamycin and cyclophosphamide (AC; 37 cycles), docetaxel (DTX; 26 cycles) and docetaxel and cyclophosphamide (TC; eight cycles). Among those patients, suspected COVID-19 symptoms were observed in only one of 62 cycles of the three regimens (1.6%) with PEG-GCSF compared to two of nine cycles (22.2%) without PEG-GCSF (p=0.0405). However, because none developed COVID-19 infection during chemotherapy, we could not assess COVID-19 severity and PEG-GCSF use. CONCLUSION: A potential role of PEG-GCSF in reducing suspected COVID-19 symptoms during chemotherapy, reducing the anxiety and need for hospital visits, thus improving patients' quality of life, is suggested. These insights could contribute to optimizing the care of breast cancer patients in situations like the current pandemic.

Sysmex XN-HPC: study of reference intervals and clinical decision limits in healthy allogeneic donors mobilised with G-CSF.

The Sysmex XN series haematopoietic progenitor cell (XN-HPC) is a novel tool for assessing stem cell yield before allogeneic haematopoietic stem cell transplantation. This study aimed to establish a reference interval (RI) for XN-HPC in peripheral blood allogeneic transplant donors following granulocyte colony-stimulating factor (G-CSF) stimulation and determine its clinical significance. All specimens were analysed using Sysmex XN-20. Samples were collected and analysed using non-parametric percentile methods to define the RIs. Quantile regression was used to explore the dependency of the RIs on sex and age. Samples were included in clinical decision limits for apheresis based on receiver operating characteristic curve analysis. The non-parametrically estimated RI for XN-HPC was 623.50 (90% confidence interval [CI90%] 510.00-657.00) to 4,144.28 (CI90% 3,761.00-4,547.00). The RIs for the XN-HPC were not age-dependent but were sex-dependent. The RI for males was 648.40 (CI90% 582.00-709.00)-4,502.60 (CI90% 4,046.00-5,219.00) and for females was 490.90 (CI90% 311.00-652.00)-3,096.90 (CI90% 2,749.00-3,782.00). Comparisons based on XN-HPC values between the poor and less-than-optimal groups, good and less-than-optimal groups, and good and non-good groups had areas under the curve of 0.794 (P < 0.001), 0.768 (P < 0.001), and 0.806 (P < 0.001), respectively, indicating a good predictive value for mobilisation effectiveness. XN-HPC data exceeding 3974 × 106/L suggested that a sufficient number of stem cells could be collected clinically. Values > 5318 < 106/L indicated 100% mobilisation effectiveness. We established an RI for XN-HPC in peripheral blood allogeneic transplant donors following G-CSF stimulation and determined clinical decision thresholds for mobilisation efficiency.

Chemotherapy-induced neutropenia management in a patient with metastatic breast cancer and Shwachman-Diamond syndrome (SDS): a case report.

Background: Shwachman-Diamond syndrome (SDS) is a rare inherited bone marrow failure syndrome associated with cytopenia and the development of hematologic malignancies. Solid tumor occurrence is rare and, historically, these patients have had poor outcomes due to chemotherapy-induced myelosuppression and increased susceptibility to infections. We report the administration of cytotoxic systemic therapy with granulocyte colony-stimulating factor (G-CSF) in a patient with SDS and metastatic breast cancer. We describe the risk-benefit profile of utilizing G-CSF in managing this patient to improve her therapeutic outcome and review the prior literature. Case Description: A 41-year-old Caucasian female with SDS developed stage IV triple-positive [estrogen positive, progesterone positive, and human epidermal growth factor receptor 2 (HER2) positive] invasive ductal carcinoma of the left breast with liver metastases. She had lifelong thrombocytopenia with other hematologic parameters within normal limits, no tumor protein 53 (TP53) mutation, and no history of marrow dysplasia. Based on her underlying SDS, paclitaxel was favored over docetaxel due to the reduced risk of myelosuppression and weekly dosing schedule. Her regimen included weekly paclitaxel with trastuzumab and pertuzumab every 21 days. She experienced chemotherapy-induced neutropenia with an absolute neutrophil count of less than 1,500 leading to the utilization of G-CSF support. She received chemotherapy with twice-weekly G-CSF and did not experience severe infections. After nine cycles of therapy, she had no evidence of metastatic disease on imaging. The patient has an ongoing complete response at 18 months since treatment initiation. Conclusions: This case report describes the treatment of a patient with SDS and metastatic breast cancer with cytotoxic chemotherapy and G-CSF. G-CSF facilitated ongoing chemotherapy administration and reduced the risk of infection leading to an optimal therapeutic outcome. There should be careful consideration of early G-CSF use in patients with SDS to optimize continuous chemotherapy dosing.

Upregulation of MMPs in placentas of patients with gestational diabetes mellitus: Involvement of the PI3K/Akt pathway.

In recent years, there has been a notable rise in the incidence of pregnancies complicated by gestational diabetes mellitus (GDM), characterized by glucose intolerance first identified during pregnancy. Analysis of placental tissue has revealed that placentas from women with GDM tend to be larger and heavier compared to control placentas, indicating potential changes in trophoblast proliferation, differentiation, and apoptosis. In this study, transcriptome sequencing was conducted on placentas obtained from both normal pregnancies and pregnancies with GDM to investigate the molecular mechanisms underlying this condition. The original sequencing data were subjected to sequencing analysis, resulting in the identification of 935 upregulated genes and 256 downregulated genes. The KEGG and GO analysis techniques on differential genes uncovered evidence suggesting that the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway may contribute to the pathogenesis of GDM. Subsequent analysis indicated that the expression levels of matrix metalloproteinases (MMP) 11, MMP12, MMP14, and MMP15, which are regulated by the PI3K/Akt pathway, were upregulated in the placentas of patients with GDM when compared to those of individuals with normal placental function. Additionally, our investigation into alternative splicing patterns revealed an increase in exon skipping alternative splicing of CSF3R in the placenta of patients with GDM compared to that in the control group. The CSF3R-PI3K-MMP pathway is speculated to regulate the pathogenesis of GDM.

Analysis of a lung cancer case with transient pseudo hypoglycemia after PEG-rhG-CSF treatment.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) is an effective treatment for chemotherapy-induced neutropenia. However, it can also induce various adverse effects, including fever, bone pain, and other discomforts arising from the abnormal proliferation of blood cells. This study presents an analysis of a case involving a middle-aged patient with small cell lung cancer who exhibited transiently low blood glucose levels without experiencing any symptoms of hypoglycemia following PEG-rhG-CSF treatment. After thorough evaluation by clinicians and pharmacists, the condition was diagnosed as pseudohyperglycemia, a phenomenon distinct from true hyperglycemia. The article provides a pharmaceutical perspective on the contributing factors, mechanisms, and management strategies for pseudohypoglycemia, offering valuable insights for clinical practice.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography revealed the course of granulocyte-colony stimulating factor-associated aortitis: A case report.

A 72-year-old man with diffuse large B-cell lymphoma underwent fluorine-18 fluorodeoxyglucose (FDG) PET/CT, revealing lymphoma lesions and no evidence of aortitis. The patient received chemotherapy and was treated with granulocyte colony-stimulating factor (G-CSF) for neutropenia. During chemotherapy, the patient underwent PET/CT again, revealing FDG accumulation and wall thickening at the aortic arch, which suggested aortitis. The patient was only experiencing fatigue. G-CSF-associated aortitis was suspected, and the original G-CSF was switched to another G-CSF while continuing chemotherapy. Three months later, the third round of PET/CT showed that FDG accumulation and wall thickening of the aortic arch vanished. PET/CT may be useful for not only the diagnosis but follow-up of G-CSF-associated aortitis. Radiologists should recognize incidental aortitis on PET/CT in patients receiving G-CSF administration.

Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. METHODS: We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS ≥ 12 months). RESULTS: Fifty patients (76.9%) received ≥ 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9 months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4 months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of ≥ 1 dose of pegfilgrastim, or either ≥ 5 doses of filgrastim or ≥ 1 dose of pegfilgrastim). CONCLUSIONS: G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC.

The Efficiency of Introducing Intrauterine Infusion of Autologous Platelet-Rich Plasma versus Granulocyte Colony-Stimulating Factor in Repeated Implantation Failure Patients: An Unblinded Randomised Clinical Trial.

BACKGROUND: Repeated implantation failure (RIF) refers to the condition where high quality embryos are unable to successfully implant after multiple cycles of in vitro fertilization (IVF) treatment. The aim of this study is to investigate the impact of intrauterine granulocyte colony-stimulating factor (G-CSF) and platelet-rich plasma (PRP) on pregnancy rate in patients with RIF. MATERIALS AND METHODS: The present randomised clinical trial study was conducted at the IVF Centre of Mehr Medical Institute in Rasht, Iran, from 2020 to 2022. The research consisted of 200 individuals who had experienced multiple failed cycles. These patients were randomised into two groups: intrauterine infusion of 1 ml of G-CSF and intrauterine infusion of 1 ml autologous PRP at least 48 hours before embryo transfer (ET). The groups were compared in terms of implantation rate, and chemical, clinical, and ongoing pregnancy. RESULTS: The implantation rate was significantly higher in patients who received PRP (P=0.016). Chemical pregnancy in the PRP group was significantly higher than G-CSF group (P=0.003). Both clinical pregnancy and ongoing pregnancy rates were significantly higher in the PRP group (P=0.001) compared to the G-CSF group (P=0.02). CONCLUSION: The utilisation of PRP via intrauterine infusion is considerably more successful than G-CSF in enhancing pregnancy and live birth rates among patients with RIF.

[Effect of Intrauterine Perfusion of Granulocyte Colony-Stimulating Factor on Endometrium and Blood Flow Parameters in Patients With Thin Endometrium: A Prospective Controlled Clinical Trial]. / å®«è ”çŒæ³¨ç²’ç»†èƒžé›†è½åˆºæ¿€å› å­æ”¹å–„è–„åž‹å­å®«å† è†œæ‚£è€ å† è†œåŠè¡€æµå‚æ•°çš„å‰çž»æ€§ä¸´åºŠå¯¹ç §è¯•éªŒ.

Objective: To investigate the effects of intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF) on the endometrial thickness, volume, and blood flow parameters of patients with thin endometrium and their clinical outcomes. Methods: We designed a prospective non-randomized synchronous controlled trial and recruited patients with thin endometrium who underwent frozen-thawed embryo transfer (FET) at Mianyang Central Hospital between September 1, 2021 and September 1, 2023. They were divided into two groups, an experimental group of patients who received the experimental treatment of intrauterine perfusion with G-CSF and a control group of patients who did not receive the experimental treatment. The general data and the clinical outcomes of the two groups were analyzed and compared. The endometrial thickness, volume and blood flow parameters of patients in the experimental group before and after intrauterine perfusion with G-CSF were analyzed. Results: The clinical data of 83 patients were included in the study. The experimental group included 51 cases, while the control group included 31 cases. There were no significant differences in the baseline data between the two groups. The clinical pregnancy rate of the experimental group (56.86%) was higher than that of the control group (50.00%) and the rate of spontaneous abortion in the experimental group (27.59%) was lower than that in the control group (37.50%), but the differences were not statistically significant (P>0.05). In the experimental group, the postperfusion endometrial thickness ([0.67±0.1] cm) was greater than the preperfusion endometrial thickness ([0.59±0.09] cm), the postperfusion ([1.84±0.81] cm3) was greater than the preperfusion endometrial volume ([1.54±0.69] cm3), and the postperfusion vascularization flow index (VFI) (1.97±2.82) was greater than the preperfusion VFI (0.99±1.04), with all the differences being statistically significant (P<0.05). Conclusion: Intrauterine perfusion with G-CSF can enhance the endometrial thickness, volume, and some blood flow parameters in patients with thin endometrium.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

The impact of G-CSF on mouse immune cells in alcoholic liver disease, focusing on variations in T cells and their subsets.

Alcoholic liver disease (ALD) significantly affects immune cell function and leads to immunological dysregulation. This study explored the potential of granulocyte colony-stimulating factor (G-CSF) to mitigate the negative effects of alcohol on immune cells in a mouse model of ALD. To investigate the capacity of G-CSF, ALD was induced using a 17-day alcohol-enriched diet, followed by a single G-CSF dose prior to sampling. We focused on the dynamics of peripheral blood mononuclear cells using high-dimensional mass cytometry to detect subtle changes. Alcohol intake reduced the number of B cells, monocytes, dendritic cells, and NK cells while increasing the number of T cells. Notably, G-CSF treatment reversed the alcohol-induced increase in total CD4+ and CD8+ T cell populations. This effect was remarkable in naïve, effector CD4+ T cells and naïve CD8+ T cells. PhenoGraph and FlowSOM analysis further revealed the recovery effect of G-CSF on specific T cell subgroups, including central memory CD8+ T cells and double-negative T cells expressing Ly6chighCD44high, which are adversely affected by alcohol. These results enhance our understanding of the effect of ALD on immune function and suggest that G-CSF is a potential therapeutic agent, laying the foundation for future clinical research.