A clinical study of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent chemoradiotherapy of cervical cancer
BMC cancer. 2021;21(1):661
PURPOSE To evaluate the effectiveness and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during chemoradiotherapy in patients with cervical cancer. METHODS From August 2018 to April 2020, 60 patients who were pathologically confirmed as cervical cancer were randomly divided into two groups at a ratio of 2:1: PEG-modified-rhG-CSF experimental group and control group. The primary endpoints were the incidence of grade 3-4 neutropenia. Secondary endpoints included the duration of grade 3-4 neutropenia, the incidence of grade 4 neutropenia, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, time to complete radiotherapy and safety. RESULTS The incidence of grade 3-4 neutropenia in the experimental group was significantly lower than the control group (10% vs. 77.78%, P < 0.001). However, there was no statistical significance between the two groups in the duration of grade 3-4 neutropenia (3.75 days vs. 5.07 days, P = 0.871). The experimental group was better than the control group in the incidence of grade 4 neutropenia, the incidence of FN and delay rate of chemotherapy, and the difference was statistically significant (P < 0.05). Besides, the prolonged time of chemotherapy and the time to complete radiotherapy in the experimental group were less than those in the control group, but the difference was not statistically significant (P > 0.05). The incidence of adverse events in the experimental group and control group were 55.00 and 94.44%, respectively, and the difference was statistically significant (P = 0.003). CONCLUSION PEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy for patients with cervical cancer can reduce the incidence of neutropenia and improve the incidence of delayed chemotherapy cycles. TRIAL REGISTRATION ClinicalTrials.gov , NCT04542356 . Registered 9 September 2020 - Retrospectively registered.
Randomized trial of granulocyte colony-stimulating factor for spinal cord injury
Brain : a journal of neurology. 2021
Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population.
A multi-centre study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of docetaxel-cyclophosphamide induced febrile neutropenia
Breast (Edinburgh, Scotland). 2021;58:42-49
BACKGROUND Primary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. METHODS EBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. RESULTS 458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = -6.7%, 95%CI = -13.5%-0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p < 0.001). Non-FN treatment-related hospitalisation occurred in 40/228 (17.5%) of ciprofloxacin patients vs 28/230 (12.2%) of G-CSF patients (p = 0.12). There were no differences in other secondary outcomes. G-CSF was associated with an incremental cost-effectiveness ratio of C$1,760,796 per one quality-adjusted life year gained. CONCLUSION The primary endpoint of superiority of G-CSF over ciprofloxacin was not demonstrated. While there were reduced FN rates with G-CSF, there were no differences in chemotherapy dose delays/reductions or discontinuations. With the commonly used willingness to pay value of C$50,000/QALY, G-CSF use was not cost-effective compared to ciprofloxacin and deserves scrutiny from the payer perspective.
The BlastGen study: a randomized controlled trial of blastocyst media supplemented with granulocyte-macrophage colony-stimulating factor
Reprod Biomed Online. 2020
RESEARCH QUESTION Does Embryogen(R)/BlastGen culture medium improve live birth rates compared with standard culture medium for women undergoing IVF and intracytoplasmic sperm injection (ICSI) with poor prognosis. DESIGN Randomized clinical trial. A total of 100 couples undergoing IVF/ICSI were randomly allocated to having their inseminated oocytes incubated in either Embryogen(R)/BlastGen sequential culture media or standard Cleavage/Blastocyst sequential culture media for 5 days (ClinicalTrials.gov Identifier: NCT02305420). RESULTS No statistically significant difference in live birth rate was found between the control group and the Embryogen(R)/BlastGen group (17 [34%] versus 11 [22%], respectively) (OR 0.55; 95% CI 0.22 to 1.32; P=0.18). After adjustment for maternal age, body mass index and fertilization procedure, the blastulation rate reduced (40.6 +/- 26.5 versus 24.6 +/- 26.7; RR 0.70, CI 0.52 to 0.95; P < 0.05), and grade of the embryo transferred (OR 0.35, CI 0.16 to 0.77; P < 0.01) when Embryogen(R)/BlastGen medium was used. CONCLUSION A significant reduction in day-5 embryo outcome parameters was found using Embryogen(R)/BlastGen compared with standard medium, and insufficient evidence of a difference in pregnancy outcomes. Taking into consideration the small samples size, study limitations and strict inclusion criteria of this single-centre study, further research is needed to determine the efficacy of Embryogen(R)/BlastGen medium in couples undergoing IVF/ICSI.
Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a six month phase II randomized study with 24 months of follow-up
Orphanet J Rare Dis. 2020;15(1):174
BACKGROUND Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited. METHODS In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed. RESULTS There were 36 patients (19 in the treatment group, 17 in the control group) included. There were no significant differences in the primary endpoints as measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline values to the values obtained during treatment or during the following 18-month non-treatment observation period [control group vs. treatment group: 0.51 +/- 12.09 mmHg vs. -0.35 +/- 13.76 mmHg, p = 0.848 (3 month); 1.85 +/- 11.21 mmHg vs. 7.31 +/- 8.81 mmHg, p = 0.146 (6 months); 6.05 +/- 11.14 mmHg vs. 6.61 +/- 10.64 mmHg, p = 0.899 (24 months)]). Percentage of diffusion capacity predicted (DLCO%) and percentage of total lung capacity predicted (TLC%), however, were significantly improved in the treatment group by the end of the study (P = 0.010 and 0.027). St. George Respiratory questionnaire (SGRQ) scores were better after 6 months treatment with GM-CSF compared to the control group, and the benefits of treatment were maintained throughout the observation period. No severe side effects were observed during the study. CONCLUSION Six months of inhaled GM-CSF treatment had no effect on the alveolar-arterial oxygen gradient in patients with mild to moderate pulmonary alveolar proteinosis. There were changes in some clinical or laboratory measures, but no clinically important changes were noted at the end of study. (Clinical Trial Registry: NCT02243228, Registered on September 17, 2014, https://www.clinicaltrials.gov/ct2/show/NCT02243228?term=NCT02243
Therapeutic role of granulocyte macrophage colony-stimulating factor (GM-CSF) in patients with persistent thin endometrium: A prospective and randomized study
Int J Gynaecol Obstet. 2020
OBJECTIVE To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on unresponsive thin (<7 mm) endometrium in women undergoing frozen-thawed embryo transfer. METHODS A single-center, randomized, prospective study enrolled 304 women with thin unresponsive endometrium from Shanghai Ninth People's Hospital between March 2017 and May 2018. Of them, 161 patients received an intrauterine infusion of GM-CSF and 143 patients served as controls. After hysteroscopy, a gel-with or without GM-CSF-was administered to fill the uterine cavity completely or up to 5 mL only. The primary outcome was confirmed pregnancy and secondary outcomes included endometrial thickness and implantation rate. RESULTS Patients who were administered GM-CSF had a significantly higher chemical pregnancy rate (35.3% vs 20.0%; P=0.009) and clinical pregnancy rate (28.6% vs 13.3%; P=0.005) compared with patients in the control group. Patients treated with GM-CSF had significantly higher endometrial thickness compared with controls (7.83+/-1.45 mm vs 7.37+/-0.70 mm, P=0.003). CONCLUSION GM-CSF therapy can effectively increase endometrial thickness and improve the clinical pregnancy rate in patients with persistent thin endometrium. The therapeutic role of GM-CSF for infertile women under in vitro fertilization and embryo transfer (IVF-ET) treatment can be further explored.
The Effects of Recombinant Human Granulocyte Macrophage Colony-stimulating Factor Gel on Third Degree Frostbite Wounds in Northeastern China: A Randomized Controlled Trial
Journal of burn care & research : official publication of the American Burn Association. 2020
The aim of the study was to investigate the effects of the rhGM-CSF gel on third degree frostbite wounds. 62 patients who had suffered third degree frostbite on their hand or foot (91 wounds in total ) were selected using a convenience sampling method and randomly allocated to two groups: the rhGM-CSF group(31patients,45 frostbite wounds) received the rhGM-CSF gel when wound dressing change daily, however, the control group (31patients, 46 frostbite wounds) received aloe glue. The wound healing time , the score of inflammation about the wound and the positive bacterial culture of wound secretions was used to measure outcomes respectively. Data were analyzed using SPSS (25.0), student's t test or Mann-Whitney U test and Chi-square test or Fisher exact test were selected, as appropriate. The healing time of the rhGM-CSF group was (12.2+/-5.0) days, which was significantly shorter than that of the control group (15.5+/-4.7) days (P <0.0001). The rhGM-CSF group's wound inflammation scores on the 7th and 14th day of treatment were (0.96+/-0.21) and (1.88+/-0.29) respectively, which were better than those of the control group (1.12+/-0.24) and (1.38+/-0.15) (both P <0.0001). The positive bacterial culture of wound secretions in the rhGM-CSF group was also better than that in the control group on the 3rd , 7th and 14th day after treatment (P =0.027, 0.004, 0.030 respectively). According to the results, using rhGM-CSF gel considerably increases the speed of frostbite wounds healing, and have an effect on protecting third degree frostbite wounds regarding the positive effects.
Multiple Cycles of Granulocyte Colony Stimulating Factor Increase Survival Times of Patients With Decompensated Cirrhosis in a Randomized Trial
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2020
BACKGROUND & AIMS There is controversy over inclusion of granulocyte colony stimulating factor (G-CSF) in treatment of decompensated cirrhosis. Previous studies tested only a single cycle of G-CSF administration or were underpowered to detect changes in survival time. We performed an adequately powered study to determine whether multiple cycles of G-CSF increase survival of patients 1 year after the start of therapy. METHODS We conducted an open-label trial of 100 patients with decompensated cirrhosis without acute-on-chronic liver failure at a tertiary centre from July 2016 through June 2018. The patients were randomly assigned to a group given 5 days of G-CSF every 3 months, with standard medical therapy, in 4 cycles (group A, n=50) or standard medical therapy alone (group B, n=50). The primary outcome was survival for 12 months after treatment began. Secondary outcomes were increase in number of CD34+ cells at day 6 compared with day 0, along with reductions in Child Turcotte Pugh and model for end-stage liver disease scores, increased control of ascites, reduced decompensation and episodes of infection, fewer hospitalizations, lower liver stiffness measurements, increased quality of life and nutrition, fulfilment of liver transplant criteria, and fewer adverse events at 12 months after the start of treatment. RESULTS Groups A and B were comparable at baseline. Survival at 12 months after initiation of treatment was significantly higher in group A (74%) than group B (42%) (P<.001). Blood samples from patients in group A had significantly more CD34+ cells on day 6 than on day 0 (P<.001); there was no significant change in group B. Compared with patients in group B, patients in group A had significant reductions in Child Turcotte Pugh and model for end-stage liver disease scores, increased ascites control, fewer infections and hospitalizations, lower liver stiffness measurements, an increased quality of life, and a lower number fulfilled the liver transplant criteria (P<.05). There was no improvement in nutrition in either group, compared with baseline. G-CSF was safe and well tolerated. CONCLUSIONS Administration of multiple cycles of G-CSF increases numbers of hematopoietic stem cells and survival of patients with decompensated cirrhosis receiving standard medical treatment. Addition of G-CSF to medical treatment might provide a bridge to liver transplantation for these patients. ClincialTrials.gov no: NCT03415698.
Granulocyte colony-stimulating factor for alcoholic hepatitis: A systematic review and meta-analysis of randomised controlled trials
JHEP reports : innovation in hepatology. 2020;2(5):100139
BACKGROUND & AIMS Granulocyte 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. METHODS This is a meta-analysis of randomised controlled trials evaluating the risk of death at 90 days and the risk of infection. RESULTS Seven 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; I (2) = 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, I (2) = 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, I (2) = 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, I (2) = 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, I (2) = 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. CONCLUSIONS Granulocyte 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 SUMMARY The 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.
GM-CSF (granulocyte macrophage colony-stimulating factor) supplementation in culture media for women undergoing assisted reproduction
Cochrane Database Syst Rev. 2020;7:Cd013497
BACKGROUND GM-CSF (granulocyte macrophage colony-stimulating factor) is a growth factor that is used to supplement culture media in an effort to improve clinical outcomes for those undergoing assisted reproduction. It is worth noting that the use of GM-CSF-supplemented culture media often adds a further cost to the price of an in vitro fertilisation (IVF) cycle. The purpose of this review was to assess the available evidence from randomised controlled trials (RCTs) on the effectiveness and safety of GM-CSF-supplemented culture media. OBJECTIVES To assess the effectiveness and safety of GM-CSF-supplemented human embryo culture media versus culture media not supplemented with GM-CSF, in women or couples undergoing assisted reproduction. SEARCH METHODS We used standard methodology recommended by Cochrane. We searched the Cochrane Gynaecology and Fertility Group Trials Register, CENTRAL, MEDLINE, Embase, CINAHL, LILACS, DARE, OpenGrey, PubMed, Google Scholar, and two trials registers on 15 October 2019, checked references of relevant papers and communicated with experts in the field. SELECTION CRITERIA We included RCTs comparing GM-CSF (including G-CSF (granulocyte colony-stimulating factor))-supplemented embryo culture media versus any other non-GM-CSF-supplemented embryo culture media (control) in women undergoing assisted reproduction. DATA COLLECTION AND ANALYSIS We used standard methodological procedures recommended by Cochrane. The primary review outcomes were live birth and miscarriage rate. The secondary outcomes were clinical pregnancy, multiple gestation, preterm birth, birth defects, aneuploidy, and stillbirth rates. We assessed the quality of the evidence using GRADE methodology. We undertook one comparison, GM-CSF-supplemented culture media versus culture media not supplemented with GM-CSF, for those undergoing assisted reproduction. MAIN RESULTS We included five studies, the data for three of which (1532 participants) were meta-analysed. We are uncertain whether GM-CSF-supplemented culture media makes any difference to the live-birth rate when compared to using conventional culture media not supplemented with GM-CSF (odds ratio (OR) 1.19, 95% confidence interval (CI) 0.93 to 1.52, 2 RCTs, N = 1432, I(2) = 69%, low-quality evidence). The evidence suggests that if the rate of live birth associated with conventional culture media not supplemented with GM-CSF was 22%, the rate with the use of GM-CSF-supplemented culture media would be between 21% and 30%. We are uncertain whether GM-CSF-supplemented culture media makes any difference to the miscarriage rate when compared to using conventional culture media not supplemented with GM-CSF (OR 0.75, 95% CI 0.41 to 1.36, 2 RCTs, N = 1432, I(2) = 0%, low-quality evidence). This evidence suggests that if the miscarriage rate associated with conventional culture media not supplemented with GM-CSF was 4%, the rate with the use of GM-CSF-supplemented culture media would be between 2% and 5%. Furthermore, we are uncertain whether GM-CSF-supplemented culture media makes any difference to the following outcomes: clinical pregnancy (OR 1.16, 95% CI 0.93 to 1.45, 3 RCTs, N = 1532 women, I(2) = 67%, low-quality evidence); multiple gestation (OR 1.24, 95% CI 0.73 to 2.10, 2 RCTs, N = 1432, I(2) = 35%, very low-quality evidence); preterm birth (OR 1.20, 95% CI 0.70 to 2.04, 2 RCTs, N = 1432, I(2) = 76%, very low-quality evidence); birth defects (OR 1.33, 95% CI 0.59 to 3.01, I(2) = 0%, 2 RCTs, N = 1432, low-quality evidence); and aneuploidy (OR 0.34, 95% CI 0.03 to 3.26, I(2) = 0%, 2 RCTs, N = 1432, low-quality evidence). We were unable to undertake analysis of stillbirth, as there were no events in either arm of the two studies that assessed this outcome. AUTHORS' CONCLUSIONS Due to the very low to low quality of the evidence, we cannot be certain whether GM-CSF is any more or less effective than culture media not supplemented with GM-CSF for clinical outcomes that reflect effectiveness and safety. It is important that independent information on the available evidence is made accessible to those considering using GM-CSF-supplemented culture media. The claims from marketing information that GM-CSF has a positive effect on pregnancy rates are not supported by the available evidence presented here; further well-designed, properly powered RCTs are needed to lend certainty to the evidence.