Efficacy Of Granulocyte Colony-stimulating Factor Research Articles

Optimized high-dose granulocyte transfusions for the treatment of infections in neutropenic patients: A single-center retrospective analysis.

Granulocyte transfusions for patients with prolonged neutropenia and severe infections has been a controversial practice. Previous studies suggest a benefit of high-dose granulocyte transfusions (≥0.6 × 109/kg), although, until recently, the consistent production of high-dose units has been challenging. Here, we present our experience and results utilizing high-dose granulocyte transfusions at a large, tertiary academic medical center for the treatment of infections in adult, neutropenic patients. A retrospective chart review (2018-2021) was conducted for all patients who received high-dose granulocyte transfusions from donors stimulated with granulocyte colony-stimulating factor (G-CSF) and dexamethasone. Gathered parameters included patient demographics, clinical history, infection status, dose, clinical outcomes, pre- and post-absolute neutrophil count (ANC), and transfusion times including time between granulocyte collection, administration, and posttransfusion ANC count. Gathered parameters were summarized using descriptive statistics, outcomes were assessed utilizing Kaplan-Meier curves/log-rank/regression testing. Totally 28 adult, neutropenic patients refractory to antimicrobial agents and/or G-CSF received a total of 173 granulocyte concentrates. Median ANC increased from 0.7 × 109/L pre-transfusion to 1.6 × 109/L posttransfusion. The mean granulocyte yield was 77.4 × 109 resulting in an average dose per kilogram of 0.90 × 109 ± 0.30 × 109 granulocytes. Composite day 42 survival and microbial response was 42.9% (n = 12/28) without significant adverse reactions. Here, we demonstrate the successful and safe implementation of high-dose granulocyte transfusions for neutropenic patients. Given the rapid and consistent production, distribution, and improved granulocyte quality, further investigations to determine the clinical efficacy of G-CSF primed granulocyte transfusions is now possible.

Granulocyte-Colony Stimulating Factor Improves Neurological and Functional Outcomes in Patients With Traumatic Incomplete Spinal Cord Injuries: A Systematic Review With Meta-Analyses.

Spinal cord injury (SCI) is a cause for significant morbidity, often resulting in long-term disability. We compared outcomes after administration of granulocyte-colony stimulating factor (G-CSF) versus controls. MEDLINE, Embase, and Cochrane Library database searches yielded 222 records; six met study inclusion criteria. Fixed-effect and random-effects models were used to establish odds ratios (ORs) and mean difference (MD) with 95% confidence intervals (CIs) for each outcome. The results of the pooled analysis showed that in patients with incomplete SCI, G-CSF resulted in increased American Spinal Cord Injury Association (ASIA) motor scores at 3 months (MD = 0.57 [95% CI = 0.04, 1.10], I 2 = 63.84%, p = 0.036), 6 months (MD = 4.18 [95% CI = 0.55, 7.80], I 2 = 98.75%, p = 0.024), change in ASIA pinprick scores at 6 months (MD = 3.38 [95% CI = 1.48, 5.28], I 2 = 89.78%, p < 0.001), and increased Spinal Cord Independence Measure (SCIM) III score at 6 months (MD = 3.27 [95% CI = 1.13, 5.41], I 2 = 91.86%, p = 0.003). G-CSF resulted in more adverse events than the non-MP control groups (OR = 1.44 [95% CI = 0.38, 2.50], I 2 = 0%, p = 0.008), but fewer than the MP control groups (OR = -4.2 [95% CI = -5.72, -2.68], I 2 = 0%, p < 0.001). Systemic white blood cell count increased after administration of G-CSF in comparison to baseline (MD = 3.57 [95% CI = 2.79, 4.35], I 2 = 55.06%, p < 0.001). G-CSF did not statistically increase ASIA Impairment Scale at 3 months (MD = 0.48 [95% CI = -0.33, 1.28], I 2 = 0%, p = 0.246) or at 6 months (MD = 1.84 [95% CI = -0.10, 3.79], I 2 = 50.09%, p = 0.063). These meta-analyses of six studies suggest that G-CSF for the treatment of incomplete SCI may result in improved neurological outcomes when compared to the controls. The results are limited by a small sample size with heterogeneity between studies. More robust prospective, randomized studies are necessary to help inform the safety and efficacy of G-CSF.

The efficacy and safety of granulocyte colony-stimulating factor in the treatment of acute-on-chronic liver failure: A systematic review and meta-analysis.

The safety and efficacy of granulocyte-colony stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain controversial. This meta-analysis aimed to evaluate the effectiveness and safety of G-CSF in treating ACLF. The estimated pooled risk ratio (RR) and 95% confidence interval (CI) assessed the treatment effects of G-CSF. Mean differences (MD) and 95% confidence intervals were used to analyze continuous data. Heterogeneity was explored by sensitivity analysis. Potential publication bias was assessed using Egger's test. Ten studies, comprising a total of 603 participants, were included in the analysis. The G-CSF group showed significantly lower MELD scores at 7-day (MD = -2.39, 95%CI: -3.95 to -0.82), CTP scores at 7-day (MD = -0.77, 95%CI: -1.41 to -0.14), and MELD scores at 30-day (MD = -3.01, 95%CI: -5.36 to -0.67) compared to the control group. Furthermore, the G-CSF group was associated with a reduced risk of sepsis (RR = 0.53, 95%CI: 0.35-0.80). The 30-day survival (RR = 1.26, 95%CI:1.10-1.43), 60-day survival (RR = 1.47, 95%CI:1.17-1.84, and 90-day survival (RR = 1.73, 95%CI: 1.27-2.35) of patients with ACLF treated with G-CSF were significantly higher than those of the control group. Our meta-analysis suggests that G-CSF therapy may be a promising treatment for ACLF, with significant improvements in liver function and survival rates, however, further studies are needed to verify this conclusion.

Efficacy of Granulocyte Colony-Stimulating Factor in Acute on Chronic Liver Failure: A Systematic Review and Survival Meta-Analysis.

Acute-on-chronic liver failure (ACLF) mostly occurs when there is an acute insult to the liver in patients with pre-existing liver disease, and it is characterized by a high mortality rate. Various therapeutic approaches have been used thus far, with orthotopic liver transplantation being the only definitive cure. Clinical trials and meta-analyses have investigated the use of granulocyte colony-stimulating factor (G-CSF) to mobilize bone marrow-derived stem cells. Some studies have suggested that G-CSF may have a significant role in the management and survival of patients with ACLF. However, the results are conflicting, and the efficacy of G-CSF still needs to be confirmed. The aim was to assess the efficacy of G-CSF in patients with ACLF. Electronic databases were searched until May 2023 for randomized controlled trials investigating the use of G-CSF in adult patients with ACLF. Outcome measures were the effects of G-CSF on overall survival, changes in liver disease severity scores, complications of cirrhosis, other G-CSF-related adverse effects, and all-cause mortality. The study's protocol has been registered with Prospero (CRD42023420273). Five double-blind randomized controlled trials involving a total of 421 participants met the inclusion criteria. The use of G-CSF demonstrated a significant effect on overall survival (HR 0.63, 95% CI 0.41 to 0.95, and I2 48%), leading to a decreased mortality (LogOR-0.97, 95% CI -1.57 to -0.37, and I2 37.6%) and improved Model for End-Stage Liver Disease (MELD) scores (SMD -0.87, 95% CI -1.62 to -0.13, and I2 87.3%). There was no correlation between the improvement of the Child-Pugh score and the use of G-CSF(SMD -2.47, 95% CI -5.78 to 0.83, and I2 98.1%). The incidence of complications of cirrhosis did not decrease significantly with G-CSF treatment (rate ratio 0.51, 95% CI 0.26 to 1.01, and I2 90%). A qualitative synthesis showed that the use of G-CSF is safe. The administration of G-CSF has demonstrated a positive impact on overall survival, liver function, and the MELD score. The presence of heterogeneity in the included studies prohibits conclusive recommendations.

Granulocyte colony stimulating factor versus human chorionic gonadotropin for recurrent implantation failure in intra cytoplasmic sperm injection: a randomized clinical trial

BackgroundRepeated implantation failure (RIF) is defined as the case whereby the transferred embryos fail to implant after several attempts of In vitro fertilization (IVF) which causes a profound impact on the quality of life and financial burden. Some clinical studies have confirmed that Granulocyte colony-stimulating factor (G-CSF) and human chorionic gonadotropin (HCG) can improve pregnancy outcomes and implantation rates. Hence, our study aims to compare the efficacy of G-CSF and HCG on pregnancy outcomes in RIF women who undergo intra-cytoplasmic sperm injection (ICSI).MethodsThis randomized, single-blinded study was conducted et al.-Azhar University Hospitals, Cairo, Egypt, between 10th October 2020 and 20th December 2020. The study included 100 women aged 20–43 years old undergoing ICSI cycles, with a history of RIF. Patients were divided randomly into two groups: group (1): included 50 patients injected with 500 IU of intrauterine HCG on embryo transfer day, and group (2): Included 50 patients injected with G-CSF on the embryo transfer day.ResultsIn 100 RIF women, we found a significant improvement in pregnancy outcomes favoring G-CSF over HCG including implantation rate, chemical pregnancy, and clinical pregnancy (P < 0.0001, P = 0.0003, and P = 0.0006, respectively).ConclusionFor the first time, we demonstrated a significant improvement in pregnancy outcomes favoring G-CSF over HCG in terms of implantation rate, chemical pregnancy, and clinical pregnancy.Trial registrationThe study was registered on Pan African Clinical Trials Registry with the following number: PACTR202010482774275 and was approved on 2nd October 2020.

Granulocyte Colony-Stimulating Factor Accelerates the Recovery of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure by Promoting M2-Like Transition of Monocytes.

Background and AimAcute-on-chronic liver failure (ACLF) has a high mortality rate. The role of granulocyte colony-stimulating factor (G-CSF) in ACLF remains controversial. Monocytes/macrophages are core immune cells, which are involved in the initiation and progression of liver failure; however, the effect of G-CSF on monocytes/macrophages is unclear. The study aimed to verify the clinical efficacy of G-CSF and explore the effect of it on monocytes in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) paitents.MethodsWe performed a large randomized controlled clinical trial for the treatment of HBV-ACLF using G-CSF. A total of 111 patients with HBV-ACLF were prospectively randomized into the G-CSF group (5 μg/kg G-CSF every day for 6 days, then every other day until day 18) or the control group (standard therapy). All participants were followed up for at least 180 days. The relationship between monocyte count and mortality risk was analyzed. The effect of G-CSF on the phenotype and function of monocytes from patients with HBV-ACLF was evaluated using flow cytometry in vivo and in vitro experiments.ResultsThe survival probability of the G-CSF group at 180 days was higher than that of the control group (72.2% vs. 53.8%, P = 0.0142). In the G-CSF-treated group, the monocyte counts on days 0 and 7 were independently associated with an evaluated mortality risk in the fully adjusted model (Model 3) [at day 0: hazard ratio (HR) 95% confidence interval (CI): 15.48 (3.60, 66.66), P = 0.0002; at day 7: HR (95% CI): 1.10 (0.50, 2.43), P=0.8080]. Further analysis showed that after treatment with G-CSF in HBV-ACLF patients, the expression of M1-like markers (HLA-DR and CD86) in monocytes decreased (HLA-DR: P = 0.0148; CD86: P = 0.0764). The expression of MerTK (M2-like marker) increased (P = 0.0002). The secretion of TNF-α, IL-6, and IL-10 from monocytes decreased without lipopolysaccharide (LPS) stimulation (TNF-α: P < 0.0001; IL-6: P= 0.0025; IL-10: P = 0.0004) or with LPS stimulation (TNF-α: P = 0.0439; P = 0.0611; IL-10: P = 0.0099). Similar effects were observed in vitro experiments.ConclusionG-CSF therapy confers a survival benefit to patients with HBV-ACLF. G-CSF can promote the anti-inflammatory/pro-restorative phenotype (M2-like) transition of monocytes, which may contribute to the recovery of ACLF.Clinical Trial Registration NumberClinicalTrials.gov, identifier (NCT02331745).

The effects of granulocyte-colony stimulating factor on chronic liver disease: a meta-analysis.

The clinical application of granulocyte-colony stimulating factor on chronic liver disease is still controversial. The study aimed to evaluate the effects of granulocyte-colony stimulating factor on chronic liver disease. A systematic literature search was performed in PubMed, Embase, Cochrane Library and Chinese Biomedical Literature database. Randomized-controlled trials assessing the efficacy of granulocyte-colony stimulating factor were selected. Granulocyte-colony stimulating factor was associated with an increasing long-term survival (RR 1.54; 95% CI 1.22 to 1.94; p = 0.0003; heterogeneity: Q = 0.26, I2 = 25%) and an increasing short-term survival (RR 1.44; 95% CI 1.16 to 1.78; p = 0.0009; heterogeneity: Q < 0.00001, I2 = 80%). Granulocyte-colony stimulating factor failed to lower mortality secondary to multiple organ failure (RR 0.65; 95% CI 0.34 to 1.21; p = 0.17; heterogeneity: Q = 0.45; I2 = 0%), gastrointestinal bleeding mortality (RR 0.97; 95% CI 0.61 to 1.56; p = 0.91; heterogeneity: Q = 0.35; I2 = 11%) and sepsis mortality (RR 0.27; 95% CI 0.06 to 1.12; p = 0.07; heterogeneity: Q < 0.00001; I2 = 90%). It significantly lowered the Child-Turcotte-Pugh (MD=-0.97, 95% CI -1.48 to -0.45; p = 0.0003; heterogeneity: Q = 0.25; I2 = 28%). No serious adverse events were observed. Granulocyte-colony stimulating factor resulted in significantly improved 12-month survival and reduced Child-Turcotte-Pugh score with relative safety. Establishment of guidelines and protocols in future clinical trials will promote granulocyte-colony stimulating factor as an effective and safe therapy for chronic liver disease.

Multiple cycles of granulocyte colony-stimulating factor in decompensated cirrhosis: a double-blind RCT.

BackgroundLiver transplant, the definitive treatment of decompensated cirrhosis (DC), is constrained by donor shortage and long-term complications. Granulocyte colony-stimulating factor (G-CSF) has been explored as an alternative option in open-label studies. This double-blind, randomized, placebo-controlled trial was designed to elucidate the efficacy of G-CSF in DC.MethodsSeventy patients were randomized to either G-CSF plus standard medical therapy (group A, n = 35) or placebo plus standard medical therapy (group B, n = 35). Primary outcome was 12-month overall survival in patients who received at least one cycle of intervention. Secondary outcomes were mobilization of CD34+ cells at day 6, improvement in Child–Turcotte–Pugh (CTP), and model for end-stage liver disease (MELD), liver stiffness measurement, quality of life, nutrition, hepatic decompensation, infection, hospitalization, and acute kidney injury.ResultsSurvival in group A was higher than that in Group B although the difference was not statistically significant (87.9% vs 66.7%; p = 0.053). CD34+ cells at day 6 were significantly higher in group A as compared to baseline (p < 0.001). Ascites control (p = 0.03) and CTP score improvement (p = 0.02) were better in group A at 12-months. Encephalopathy episodes (p = 0.005), infections (p = 0.005) were fewer in group A than group B at 12 months. Other secondary outcomes did not improve post-therapy. There were no treatment-related discontinuations or severe adverse events.ConclusionsG-CSF therapy is safe. The improvement in survival at 12 months is not statistically significant. Better control of ascites, improvement of CTP score, fewer encephalopathy episodes and decreased rate of infections were observed with G-CSF therapy (NCT03911037).Trials Registration NCT03911037Supplementary InformationThe online version contains supplementary material available at 10.1007/s12072-022-10314-x.

Superior physical and mental health of healthy volunteers before and five\xa0years after mobilized stem cell donation

BackgroundSafety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally.MethodsWe enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire.ResultsBaseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time.ConclusionsHSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation.Trial registration National Clinical Trial NCT01766934

Efficacy of subcutaneous granulocyte colonystimulating factor infusion for treating thin endometrium.

ObjectiveThis study was conducted to assess the efficacy of subcutaneous granulocyte colony-stimulating factor (G-CSF) for treating thin endometrium.MethodsData from 88 infertile women with thin endometrium (<7 mm) aged 23 to 40 years were evaluated retrospectively over a period of 1 year. In group 1, subcutaneous infusion of G-CSF (300 μg/mL) was administered to 44 women along with other supplemental treatments. If the lining did not exceed 7 mm within 72 hours, a second infusion was administered. In group 2, which also had 44 women, only estradiol valerate and sildenafil were administered, while subcutaneous G-CSF infusion was not. Embryo transfers were performed once the lining exceeded 7.5 mm. The efficacy of G-CSF was evaluated by assessing the thickness of the endometrium before embryo transfer, pregnancy rates, and clinical pregnancy rates.ResultsThere were no differences between the groups regarding demographic variables, egg reserves, sperm parameters, the number of embryos transferred, and embryo quality. The pregnancy rate was significantly higher in group 1 (60%, 24 of 40 cases) than in group 2 (31%, 9 of 29 cases) (p<0.001). The clinical pregnancy rate was also significantly higher in group 1 (55%) than in group 2 (24%) (p<0.001).ConclusionSubcutaneous G-CSF infusion improved the thickness of the endometrium when it was thin. To the best of our knowledge, this is the first documented study to clearly demonstrate the benefits of subcutaneous G-CSF infusion for treating thin endometrium.

From the Editor’s Desk...

Acute-on-chronic liver failure (ACLF) develops in patients with decompensated liver cirrhosis and is characterised by organ failure and poor prognosis. Granulocyte-colony stimulating factor (G-CSF) has been proposed for the treatment of patients with ACLF. In this first multicentre prospective, controlled, open-label phase II study, Engelmann et al. aimed to evaluate the safety and efficacy of G-CSF in ACLF. Unfortunately, G-CSF did not improve 90-day survival compared to standard medical therapy (34.1% vs.

Effectiveness of granulocyte colony-stimulating factor for patients with acute-on-chronic liver failure: a meta-analysis.

BACKGROUND: The safety and efficacy of granulocyte colony-stimulating factor (G-CSF) for the treatment of acute-on-chronic liver failure (ACLF) remain uncertain. Therefore, we conducted a meta-analysis to draw a firmer conclusion.METHODS: We searched the Cochrane library, PubMed, Embase, and China Biology Medicine disc to identify relevant RCTs performed before January 2020. Risk ratios (RRs) and their 95% confidence intervals (95% CIs) were calculated using a random effects model.MAIN OUTCOME MEASURES: RRs (95% CI) for 1-, 2-, and 3-month survival rates.SAMPLE SIZE: Six RCTs, including three open-label studies.RESULTS: The six studies included 246 subjects (121 in a G-CSF group and 125 in a control group). G-CSF administration significantly improved the 1-, 2-, and 3-month survival rates in patients with ACLF. The pooled RRs (95% CI, P) were 0.43 (0.27–0.69, P=.0004), 0.44 (0.32–0.62, P<.00001), and 0.39 (0.22–0.68, P=.0009), respectively.CONCLUSION: G-CSF may be beneficial and effective in the treatment of ACLF, but further studies are needed to verify this conclusion.LIMITATIONS: The sample size was small, and studies were restricted to countries in Asia.PROSPERO REGISTRATION NUMBER: CRD42021225681CONFLICT OF INTEREST: None.

Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study)

Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF. In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n= 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period. Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p= 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p= 0.992 and HR 1.058; 95% CI 0.727-1.548; p= 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation. In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. CLINICALTRIALS. NCT02669680 LAY SUMMARY: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.

Efficacy of Granulocyte Colony-Stimulating Factor in Established Neutropenia in Pediatric Solid Tumors

Efficacy of Granulocyte Colony-Stimulating Factor in Established Neutropenia in Pediatric Solid Tumors

Treatment of G-CSF in unexplained, repeated implantation failure: A systematic review and meta-analysis

BackgroudRepeated implantation failure (RIF) is a stressful situation for subfertile women undergoing in vitro fertilisation (IVF) treatment and caregivers. Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in assisted reproductive techniques. However, it is currently unknown whether G-CSF is effective in improving results for patients with RIF. ObjectiveTo describe and summarize current evidence of the effect of the granulocyte colony stimulating factor (G-CSF) in treating RIF. MethodRelevant scientific literature was thoroughly searched by computer in domestic and foreign database from the inceptions to November 2019. And relevant randomized controlled trials (RCTs) assessing the efficacy of G-CSF in unexplained RIF were included. The meta-analysis was conducted by Stata 12. 0 software, and we estimated relative risks (RRs) and associated 95 % confidence intervals (CIs) of G-CSF on implantation rate (IR), the clinical pregnancy rate (CPR), the abortion rate (AR) in patients with unexplained RIF using fixed-effect model. Besides, Subgroup analysis was performed according to the different administration methods. ResultA total of eleven articles were included for the final meta-analysis with sample sizes ranging from 13 to 107 patients. The G-CSF was associated with an increased IR [RR = 2.346, 95 %CI (1.615–3.409), I2 = 0. 0%] and CPR [RR = 1.910, 95 %CI (1.562–2.337), I2 = 0.0 %] in patients with unexplained RIF. When further stratified by the method of administration, the subgroup analysis revealed that both intrauterine injection and subcutaneous injection are capable of improving IR[subcutaneous injection:RR = 2.400, 95 %CI (1. 268−4. 542), I2 = 0.0 %; intrauterine injection:RR = 2.317, 95 %CI (1.462–3.673), I2 = 0.0 %] and CPR[subcutaneous injection: RR = 2. 022, 95 %CI (1.443–2.832), I2 = 0. 0%; intrauterine injeciton: RR = 1.848, 95 %CI (1.438–2.376), I2 = 0. 0%]. G-CSF was not associated with AR in patients with unexplained RIF [RR = 2.092, 95 %CI (0.815–5.369), I2 = 0.0 %]. ConclusionThe current evidence support G-CSF’s positive effect on the implantation rate and clinical pregnancy rate of patients with unexplained RIF, especially when administrated by subcutaneous injection. There is no conclusive evidence for the association between G-CSF and the abortion rate. Moreover, few of the included articles reported side effects of G-CSF, so its safety remains to be investigated.Thus, future research should evaluate.

Granulocyte colony-stimulating factor for alcoholic hepatitis: Asystematic review and meta-analysis of randomised controlled trials.

Background & AimsGranulocyte colony-stimulating factor (G-CSF) treatment has been proposed as a therapeutic option for patients with severe alcoholic hepatitis (AH). The aim of this study was to synthesise available evidence on the efficacy of G-CSF in AH.MethodsThis is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection.ResultsSeven studies were included. Of a total of 396 patients, 336 had AH, 197 patients were treated with G-CSF, and 199 received placebo or pentoxifylline. In overall meta-analysis, G-CSF therapy was associated with a reduced risk of death at 90 days (odds ratio [OR] 0.28; 95% CI 0.09–0.88; p = 0.03). There was high heterogeneity between studies (p <0.001; I2 = 80%). Five studies were performed in Asia and 2 in Europe. In the subgroup analysis of studies performed in Asia, G-CSF was associated with a reduced risk of death (OR 0.15; 95% CI 0.08–0.28; p <0.001; heterogeneity: p = 0.5, I2 = 0%). In European studies, G-CSF tended to increase mortality compared with controls, although the difference was not significant (OR 1.89; 95% CI 0.90–3.98; p = 0.09; heterogeneity: p = 0.8, I2 = 0%). In Asian studies, occurrence of infection was less frequent in G-CSF patients than in controls (OR 0.12; 95% CI 0.06–0.23; p <0.001; heterogeneity: p = 0.7, I2 = 0%), whilst in European studies, this occurrence was not statistically different (OR 0.92; 95% CI 0.50–1.68; p = 0.78; heterogeneity: p = 0.5, I2 = 0%). In sensitivity analyses, excluding studies that included patients with acute-on-chronic liver failure (ACLF) other than AH, patients with less severe AH, or patients with non-response to corticosteroids, results were similar to those of overall analyses, both for mortality and occurrence of infection.ConclusionsGranulocyte colony-stimulating factor therapy may improve the prognosis of patients with severe AH. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.Lay summaryThe main finding of this meta-analysis is that the use of granulocyte colony-stimulating factor (G-CSF) is associated with a mortality reduction of more than 70% at 3 months amongst patients with alcoholic hepatitis (AH) compared with controls who did not receive this therapy. However, owing to the high heterogeneity observed in the overall analysis caused by conflicting results between the Asian and European studies, G-CSF cannot currently be recommended for patients with AH, particularly in Europe. Whether these differences can be explained by ethnic differences or disparities in patient selection and disease severity remains unclear.

The Effects of Granulocyte Colony-Stimulating Factor in Patients with a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling: A 10-Year Follow-Up of the RIGENERA Study.

Background: the RIGENERA trial assessed the efficacy of granulocyte-colony stimulating factor (G-CSF) in the improvement of clinical outcomes in patients with severe acute myocardial infarction. However, there is no evidence available regarding the long-term safety and efficacy of this treatment. Methods: in order to evaluate the long-term effects on the incidence of major adverse events, on the symptom burden, on the quality of life and the mean life expectancy and on the left ventricular (LV) function, we performed a clinical and echocardiographic evaluation together with an assessment using the Minnesota Living with Heart Failure Questionnaire (MLHFQ) and the Seattle Heart Failure Model (SHFM) at 10-years follow-up, in the patients cohorts enrolled in the RIGENERA trial. Results: thirty-two patients were eligible for the prospective clinical and echocardiography analyses. A significant reduction in adverse LV remodeling was observed in G-CSF group compared to controls, 9% vs. 48% (p = 0.030). The New York Heart Association (NYHA) functional class was lower in G-CSF group vs. controls (p = 0.040), with lower burden of symptoms and higher quality of life (p = 0.049). The mean life expectancy was significantly higher in G-CSF group compared to controls (15 ± 4 years vs. 12 ± 4 years, p = 0.046. No difference was found in the incidence of major adverse events. Conclusions: this longest available follow-up on G-CSF treatment in patients with severe acute myocardial infarction (AMI) showed that this treatment was safe and associated with a reduction of adverse LV remodeling and higher quality of life, in comparison with standard-of-care treatment.

Granulocyte Colony Stimulating Factor in Improving Outcomes of Neonatal Sepsis: A Meta-Analysis

Background: Neonatal sepsis complicated with neutropenia increases risk of mortality by 50%. The immature neutrophil production of neonates is often overwhelmed by severe infection. Granulocyte colony stimulating factor (G-CSF), a naturally occurring cytokine used to support neutrophil recovery during chemotherapy, is a possible treatment that can improve outcomes of neonatal sepsis. Objectives: To determine the efficacy of G-CSF in decreasing mortality and morbidity in septic neonates. Methodology: Electronic searches were conducted on online journal databases. Unpublished or ongoing studies were sought in training institutions accredited by the Philippine Pediatric …

Premobilization of CD133+ cells by granulocyte colony- stimulating factor attenuates ischemic acute kidney injury induced by cardiopulmonary bypass

Ischemic acute kidney injury (IAKI) is a common but severe complication after a cardiopulmonary bypass (CPB). Multiple studies have demonstrated that peripheral CD133+ or differentiated cells are able to home and repair the damaged tissues, but the number of available CD133+ cells is limited, and no efficient method published previously to mobilize them immediately. We analyzed the relationship between CD133+ cells and renal function in CPB patients, in addition, the efficacy of granulocyte colony-stimulating factor (G-CSF) pre-mobilized CD133+ cells in treating of mouse IAKI model have been investigated. In the clinical study, the prospective cohort study analyzed the correlation between BUN/Crea level and the peripheral CD133+ cell numbers. CPB was associated with postoperative renal dysfunction. The significant negative correlation was observed between patients’ Crea and CD133+ cells (P < 0.05). The proposed mechanism studies were performed on the mouse IAKI model. The experimental mice were treated by G-CSF to mobilize CD133+ cells before implementing CPB. Data on cell count, inflammatory index, renal function/injury, and CD133+ cell mobilization were analyzed. The result demonstrated that pretreatment by G-CSF resulted in tremendous increase in the number of mouse peripheral blood and renal CD133+ cells, significantly reduces renal tissue inflammation and dramatically improves the renal function after CPB. In summary, we concluded that premobilization of CD133+ cells abated CPB induced IAKI, by promoting both repairing damaged epithelium and by its anti-inflammatory activity. Our findings stress the remarkable applications of CD133+ or differentiated cells-based therapies for potential preventing ischemic acute kidney injury.

Efficacy of granulocyte colony stimulating factor in combination with erythropoiesis stimulating agents for treatment of anemia in patients with lower risk myelodysplastic syndromes: A systematic review.

Anemic patients with lower risk myelodysplastic syndromes are frequently treated with erythropoiesis stimulating agents (ESA), eventually in combination with granulocyte colony stimulating factor (G-CSF). However, the evidence for the efficacy of a combined treatment remains controversial. The goal of our analysis was to assess the available evidence for a combined treatment. We performed a systematic review and identified only nine eligible studies. In two randomized controlled trials (n = 98), erythroid response rates were 33% and 40% after low-/standard-doses of ESA alone (10,000-30,000 rHuEPO equivalents/week) versus 65% and 73% after combination treatment. In seven trials with sequential drug administration (n = 393), erythroid response rates ranged from 12% to 71% after full-doses of ESA alone (60,000-80,000 rHuEPO equivalents/week) and from 35% to 74% after combination therapy. Our analysis supports an additional efficacy of G-CSF added to low-/standard-dose ESA, but the available data remains controversial, if G-CSF is added to full-dose ESA.