Granulocyte Colony-stimulating Factor Therapy Research Articles

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Impact of different genetic mutations on granulocyte development and G-CSF responsiveness in congenital neutropenia

AbstractCongenital neutropenia (CN) is a genetic disorder characterized by persistent or intermittent low peripheral neutrophil counts, thus increasing susceptibility to bacterial and fungal infections. Various forms of CN, caused by distinct genetic mutations, exhibit differential responses to granulocyte colony–stimulating factor (G-CSF) therapy, with the underlying mechanisms not fully understood. This study presents an in-depth comparative analysis of clinical and immunological features in 5 CN patient groups (severe congenital neutropenia [SCN]1, SCN3, cyclic neutropenia [CyN], warts, hypogammaglobulinaemia, infections and myelokathexis [WHIM], and Shwachman-Bodian-Diamond Syndrome [SBDS]) associated with mutations in ELANE, HAX1, CXCR4, and SBDS genes. Our analysis led to the identification of 11 novel mutations in ELANE and 1 each in HAX1, CXCR4, and G6PC3 genes. Investigating bone marrow (BM) granulopoiesis and blood absolute neutrophil count after G-CSF treatment, we found that SCN1 and SCN3 presented with severe early-stage disruption between the promyelocyte and myelocyte, leading to a poor response to G-CSF. In contrast, CyN, affected at the late polymorphonuclear stage of neutrophil development, showed a strong G-CSF response. WHIM, displaying normal neutrophil development, responded robustly to G-CSF, whereas SBDS, with moderate disruption from the early myeloblast stage, exhibited a moderate response. Notably, SCN1 uniquely impeded neutrophil development, whereas SCN3, CyN, WHIM, and SBDS also affected eosinophils and basophils. In addition, SCN1, SCN3, and CyN presented with elevated serum immunoglobulins, increased BM plasma cells, and higher A Proliferation-Inducing Ligand levels. Our study reveals a strong correlation between the stage and severity of granulocyte development disruption and the efficacy of G-CSF therapy.

Incidence of pulmonary toxicity in bleomycin-containing regimens for testicular cancer with and without the use of growth factor.

The concurrent use of bleomycin and granulocyte colony-stimulating factors (G-CSFs) has historically been debated as a risk factor for bleomycin-induced pulmonary toxicity in patients with both testicular cancer and Hodgkin's lymphoma. The purpose of this study is to evaluate the incidence of pulmonary toxicity in patients with testicular cancer who were treated with bleomycin and pegfilgrastim concurrently. This is a retrospective study that includes male patients over the age of 18 years old diagnosed with testicular cancer who received bleomycin-containing chemotherapy regimens with and without the use of G-CSF agents. There were a total of 33 patients identified as receiving bleomycin, with 30 of those patients having received concurrent G-CSF therapy. Of the patients who received G-CSF therapy, 11 patients (36.6%) experienced pulmonary toxicity leading to discontinuation of bleomycin or changes in chemotherapy regimens altogether. There were no major differences in patient demographics or risk factors between those who received G-CSF and developed pulmonary toxicity and those who received G-CSF but did not develop pulmonary toxicity. Further studies are needed in order to fully assess the risk of pulmonary toxicity with this chemotherapy regimen.

Chidamide, Decitabine, Cytarabine, Aclarubicin, and Granulocyte Colony-stimulating Factor Therapy for Patients with Relapsed/Refractory Acute Myeloid Leukemia: A Retrospective Study from a Single-Center.

Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia. However, their efficacy in patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains unclear. Clinical data of R/R AML patients who received a CDCAG regimen (chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor) from July 1, 2018 to October 31, 2021 at our center were retrospectively assessed, and the safety and efficacy of the CDCAG regimen were evaluated. Patients were followed up until November 30, 2021, with a median follow-up of 21.6 months (95% CI: 10.0-33.2 months). A total of 67 patients were enrolled. Two patients died within 3 weeks after the initiation, and therefore only 65 patients underwent the assement for clinical response and survival. It was found that 56.9% patients achieved complete remission with a median overall survival (OS) of 9.6 months. The median OS of responders was 25.9 months, while that of non-responders was 5.0 months (P<0.0001). Patients with gene mutations had a superior overall response rate (ORR) (80.4% vs. 45.5%, P=0.043) compared to those without gene mutations. The presence of DNA methyltransferase 3 A (DNMT3A), ten-eleven translocation-2 (TET2), and isocitrate dehydrogenase 1/2 (IDH1/2) mutations did not affect the response rate (88.2% vs. 68.9%, P=0.220) and reflected a better OS (not attained vs. 9.0 months, P=0.05). The most common non-hematologic adverse events were pulmonary infection (73.1%), followed by febrile neutropenia (23.9%) and sepsis (19.4%). The CDCAG regimen was effective and well-tolerated in R/R AML patients, increasing the potential for allogeneic hematopoietic stem cell transplantation. Moreover, patients with DNMT3A, TET2, and IDH1/2 mutations might benefit from this regimen.

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.

Acute, Chronic, and Latent Infection with (Re)Activation Melioidosis

Melioidosis can present as an acute as well as chronic disease and can be fatal. Type 2 diabetes mellitus is one of the most common risk factors for acquiring this infectious disease.We present a case of a 36-year-old diabetic male patient who presented in March 2022 with acute severe melioidosis and later developed chronic melioidosis. He did not take complete treatment and presented again in January 2023 with features of Latent infection with reactivation. The blood and pus culture showed positive results for Burkholderia pseudomallei (B. pseudomallei). The use of granulocyte colony-stimulating Factor (G-CSF) in addition to antimicrobial treatment with meropenem and later ceftazidime therapy played an effective role in the recovery of the patient. In this case report we present the acute and chronic manifestations with which he reported along with management of the case, review the literature on the impaired immunity in type 2 diabetic patient in melioidosis, latent infection with (re)activation, the suggested role of G-CSF and antimicrobial therapy.

Cyclic Neutropenia Mimicking Crohn's Disease: Two Case Reports and a Narrative Review.

Cyclic neutropenia is a rare hematological condition characterized by periodic fluctuations in neutrophil counts, with a 21-day periodicity. Clinical presentation varies from mild to severe forms of the disease, with the onset of recurrent fever, painful oral ulcers, recurrent bacterial infections, peritonitis, and septic shock. The availability of granulocyte colony-stimulating factor (G-CSF) has revolutionized the management and natural history of this disease, regulating the proliferation, differentiation, and maturation of the progenitor cells, and reducing the duration of neutropenia. Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a group of chronic pathologies that affect the gastrointestinal tract. The onset of both diseases may be at a young age (even during childhood or adolescence), and clinical manifestations may lead to misdiagnosis, due to similar characteristics such as recurrent infections, oral ulcers, perianal abscesses, and infertility. Moreover, the two pathologies are rarely associated, with different management and therapeutic options. Here, we describe two case reports of patients who underwent surgery because of diagnosis of complicated CD. After surgery, due to persistent neutropenia, the hematologist consultant confirmed suspicions of cyclic neutropenia, and G-CSF therapy was started with benefits, underlining the crucial importance of proper differential diagnosis.

Granulocyte-colony stimulating factor in decompensated liver cirrhosis: a meta-analysis of four randomized controlled trials.

Decompensated liver cirrhosis (DC) has high mortality, but liver transplantation is limited due to organ scarcity and contraindications for transplantation. Granulocyte-colony stimulating factor (GCSF) shows potential for liver disease treatment with its regenerative and immunomodulatory properties. To assess the controversial use of GCSF in DC, a meta-analysis of randomized controlled trials (RCTs) compared survival benefits in patients receiving GCSF plus standard medical therapy (SMT) versus SMT alone. A literature search was performed in four databases from data inception up to December 2022, and all registered randomized controlled (RCTs) evaluating GCSF-based therapies for cirrhotic patients were included. A study combining four RCTs assessed the impact of GCSF with SMT in 595 patients with decompensated cirrhosis. The results indicated that GCSF + SMT led to higher odds of survival compared to SMT alone [risk ratio 1.28, 95% CI (1.08-1.5)]. Heterogeneity existed among the studies, but overall, GCSF showed potential in improving survival. The intervention group exhibited improved Child-Pugh-Turcotte scores [-2.51, CI (-4.33 to -0.70)], and increased CD34 levels, but no significant improvement in MELD scores. These findings suggest GCSF may benefit patients with decompensated cirrhosis in terms of survival and liver function. These results suggest that the combination of GCSF and SMT may have a positive impact on the survival rate and improvement in CPT score in patients with DC. Further RCTs are needed to shed more light on this promising modality in end-stage liver disease.

Granulocyte colony-stimulating factor effects on neurological and motor function in animals with spinal cord injury: a systematic review and meta-analysis.

Spinal cord injury (SCI) is a severe neurological injury for which no effective treatment exists. Granulocyte colony-stimulating factor (G-CSF) is used to treat autologous bone marrow transplantation, chemotherapy-induced granulocytopenia, Acquired Immune Deficiency Syndrome (AIDS), etc. Recent research has revealed the potential application of G-CSF on neuroprotective effectiveness. In central nervous system diseases, G-CSF can be used to alleviate neuronal injury. To investigate the effects of G-CSF on Basso, Beattie, and Bresnahan (BBB) scale score, inclined plane test, electrophysiologic exam, quantitative analysis of TUNEL-positive cells, and quantitative analysis of glial fibrillary acidic protein (GFAP) immunostaining images in animal models of SCI. We searched PubMed, Web of Science, and Embase databases for all articles on G-CSF intervention with animal models of SCI reported before November 2022. A total of 20 studies met the inclusion criteria. Results revealed that G-CSF intervention could improve the BBB scale score in both groups at 3, 7, 14, 28, and 35 days [at 35 days, weighted mean differences (WMD) = 2.4, 95% CI: 1.92-2.87, p < 0.00001, I2 = 69%]; inclined plane test score; electrophysiologic exam; quantitative analysis of TUNEL-positive cell numbers; quantitative analysis of GFAP immunostaining images in animal models of SCI. Subgroup analysis revealed that treatment with normal saline, phosphate-buffered saline, and no treatment resulted in significantly different neurological function effectiveness compared to the G-CSF therapy. SD rats and Wistar rats with SCI resulted in significant neurological function effectiveness. C57BL/6 mice showed no difference in the final effect. The T9-T10 or T10 segment injury model and the T8-T9 or T9 segment injury model resulted in significant neurological function effectiveness. The BBB score data showed no clear funnel plot asymmetry. We found no bias in the analysis result (Egger's test, p = 0.42). In our network meta-analysis, the SUCRA ranking showed that 15 mg/kg-20 mg/kg was an optimal dose for long-term efficacy. Our meta-analysis suggests that G-CSF therapy may enhance the recovery of motor activity and have a specific neuroprotective effect in SCI animal models.Systematic review registration: PROSPERO, identifier: CRD42023388315.

DCM Support: cell therapy and circulatory support for dilated cardiomyopathy patients with severe ventricular impairment.

The DCM Support trial (NCT03572660) uses a percutaneous circulatory support device (Impella CP, Abiomed, Danvers, MA, USA) to improve the safety of an intracoronary cell infusion procedure in patients with dilated cardiomyopathy (DCM) and a severely reduced left ventricular ejection fraction (LVEF). DCM Support is a single-site, single-arm Phase II trial enrolling 20 symptomatic DCM patients with an LVEF≤35% despite optimal medical and device therapy. After 5days of granulocyte colony-stimulating factor therapy and a subsequent bone marrow aspiration, patients undergo an intracoronary infusion of autologous bone-marrow-derived mononuclear cells. The Impella CP device is used to provide haemodynamic support during the infusion procedure. The trial's primary endpoint is change in LVEF from baseline at 3months. Secondary efficacy endpoints are change in LVEF from baseline at 12months, and change in exercise capacity, New York Heart Association class, quality of life, and N-terminal pro-B-type natriuretic peptide levels from baseline at 3 and 12months. Safety endpoints include procedural safety and major adverse cardiac events at 3 and 12months. This is the first trial to assess the safety and efficacy of cytokine and autologous intracoronary cell therapy with a procedural circulatory support device for patients with severe left ventricular impairment. This novel combination may allow us to target a patient population most at need of this therapy.

Use of granulocyte colony-stimulating factor in patients with chemotherapy-induced neutropaenia.

Febrile neutropaenia (FN) and resultant infections are the major cause of treatment-related morbidity and mortality in patients receiving chemotherapy. Clinical practice guidelines recommend the use of granulocyte colony-stimulating factors (G-CSF) to reduce the risk of FN and ensuing complications in patients receiving chemotherapy. Despite these recommendations, inappropriate usage of G-CSF has been reported. To assess prescribing patterns and adherence to international guidelines of G-CSF in adult patients with chemotherapy-induced neutropaenia (CIN) at the haematology oncology wards of the Dr George Mukhari Academic Hospital (DGMAH) and compliance to guidelines. Medical records of adult patients who received G-CSF were reviewed retrospectively between 01 January 2018 and 31 July 2018. Of the 128 patient files screened, 57 cases met the inclusion criteria. Duration of treatment with G-CSF was not in accordance with guidelines in more than 50% of the patients and in 43.86%, G-CSF dosing deviated from recommended guidelines. The study demonstrated over-prescribing of G-CSF due to either increased doses or duration of G-CSF therapy. Although prescribed for the correct indication, the dosage was often too high or the duration was too long, even once an acceptable neutrophil nadir count was reached. Interventions to optimise the use of G-CSF are required and the pharmacist may play a role in this regard. The administration of the correct doses of G-CSF can reduce both the severity and duration of neutropaenia. Over-prescribing and incorrect dosing may contribute to patient morbidity and add to the financial burden of healthcare.

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

CD34+ progenitor cells as diagnostic and therapeutic targets in Alzheimer's disease.

Novel therapeutic approach to slow down the inflammatory cascade in acute/subacute spinal cord injury: Early immune therapy with lipopolysaccharide enhanced neuroprotective effect of combinational therapy of granulocyte colony-stimulating factor and bone-marrow mesenchymal stem cell in spinal cord injury.

Bone-marrow mesenchymal stem cells (BM-MSCs) have not yet proven any significant therapeutic efficacy in spinal cord injury (SCI) clinical trials, due to the hostile microenvironment of the injured spinal cord at the acute phase. This study aims to modulate the inflammatory milieu by lipopolysaccharide (LPS) and granulocyte colony-stimulating factor (G-CSF) to improve the BM-MSCs therapy. For this purpose, we determined the optimum injection time and sub-toxic dosage of LPS following a T10 contusion injury. Medium-dose LPS administration may result in a local anti-inflammatory beneficial role. This regulatory role is associated with an increase in NF-200-positive cells, significant tissue sparing, and improvement in functional recovery compared to the SCI control group. The second aim was to examine the potential ability of LPS and LPS + G-CSF combination therapy to modulate the lesion site before BM-MSC (1 × 105 cells) intra-spinal injection. Our results demonstrated combination therapy increased potency to enhance the anti-inflammatory response (IL-10 and Arg-1) and decrease inflammatory markers (TNF-α and CD86) and caspase-3 compared to BM-MSC monotherapy. Histological analysis revealed that combination groups displayed better structural remodeling than BM-MSC monotherapy. In addition, Basso-Beattie-Bresnahan (BBB) scores show an increase in motor recovery in all treatment groups. Moreover, drug therapy shows faster recovery than BM-MSC monotherapy. Our results suggest that a sub-toxic dose of LPS provides neuroprotection to SCI and can promote the beneficial effect of BM-MSC in SCI. These findings suggest that a combination of LPS or LPS + G-CSF prior BM-MSC transplantation is a promising approach for optimizing BM-MSC-based strategies to treat SCI. However, because of the lack of some methodological limitations to examine the survival rate and ultimate fate of transplanted BM-MSCs followed by LPS administration in this study, further research needs to be done in this area. The presence of only one-time point for evaluating the inflammatory response (1 week) after SCI can be considered as one of the limitations of this study. We believed that the inclusion of additional time points would provide more information about the effect of our combination therapy on the microglia/macrophage polarization dynamic at the injured spinal cord.

Favorable outcome of empagliflozin treatment in two pediatric glycogen storage disease type 1b patients.

Glycogen storage disease type 1b (GSD1b) is an ultra-rare autosomal recessive disorder, caused by mutations in SLC37A4 gene. Affected patients present with episodes of fasting hypoglycemia and lactic acidosis, hepatomegaly, growth retardation, hyperlipidemia and renal impairment. In addition, patients present neutropenia, neutrophil dysfunction and oral, and skin infections as well as a significant predisposition to develop inflammatory bowel disease (IBD). Low neutrophil counts and function is related to the toxic accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P). Recently, several reports have shown that off-label treatment with empagliflozin (EMPA), an inhibitor of the renal glucose transporter SGLT2, decreased blood 1,5-anhydroglucitol (1,5-AG), and neutrophil 1,5-AG6P, thus resulting in a new therapeutic option for neutropenia and neutrophil dysfunction in patients. Off-label treatment with EMPA was established in two GSD1b patients after signed informed consent. The patients were followed clinically. We monitored neutrophil counts and function, 1,5-AG levels in plasma and its renal clearance before and during EMPA treatment. A 17 year-old girl who had long standing oral ulcers and developed IBD, requiring systemic steroid and regular granulocyte colony-stimulating factor (GCSF) therapy and an 8 year-old boy who had steady non healing oral lesions were treated with empagliflozin during 18-24 months. Treatment led to increase of neutrophil counts and function with substantial clinical improvement. This included remission of IBD in the first patient which allowed to discontinue both GCSF and steroid therapy and resolution of oral lesions in both patients. The concentration of 1,5-AG in blood was greatly decreased within two weeks of treatment and remained stable thereafter. Repurposing of empagliflozin to treat neutropenia in two GSD1b patients was safe and resulted in the urinary excretion of 1,5-AG, the normalization of neutrophil function, and a remarkable improvement of neutropenia-related clinical traits. We showed for the first time that empagliflozin increases concomitantly the renal clearance of both 1,5-anhydroglucitol and glucose in GSD1b patients.

ODP496 Methimazole Induced Agranulocytosis Despite Minimal Intermittent Therapy

Abstract Introduction Anti-thyroid drugs, such as methimazole (MMI), are standard therapies for the medical management of Graves Disease. Agranulocytosis is a rare but lethal adverse effect of anti-thyroid medications. Here we discuss a case that highlights the importance of monitoring not only in the early stages of therapy, but also low dosing of therapy, intermittent therapy and even missing doses/discontinuation of therapy. Case History A 65 year-old male with past medical history of end-stage renal disease on peritoneal dialysis who presented to the hospital with syncope, ventricular tachycardia, tremulousness, weight loss of 22 pounds over 2 weeks was subsequently diagnosed with pericardial effusion with tamponade as well as hyperthyroidism. Suppressed TSH of &amp;lt; 0. 005 µIU/mL, Free T4 = 4.5 ng/dL, FT3 8.4 pg/ml, Negative TSI and TPO antibodies. He was started on methimazole 30 mg daily which he received 2 doses prior to discharge as well as beta-blocker therapy. He was re-admitted 1 week later for hypotension, nausea, vomiting and reportedly not taking any medications due to the vomiting right after last discharge supported by his hyperthyroidism being unchanged with a TSH of &amp;lt;0. 005 µIU/mL, free T4 4.21, Free T3 5.8 pg/ml. He was restarted on methimazole 3 days into admission. He received 4 days total of 30 mg daily and was discharged on methimazole 20 mg bid. He was re-admitted 8 days later, during which time again he had nausea and vomiting resulting in not taking methimazole for 1 week prior to admission, maximally 1 day of therapy. At this 3rd admission he was found to have evidence of agranulocytosis with a WBC count of 0.97×10^9 and absolute granulocyte count of 0. 06×10^9. Methimazole was held, he was started on propranolol 60 q6 and cholestyramine 4g bid. Hematology Oncology consultation indicated there would be little benefit from granulocyte colony stimulating factor therapy in medication induced agranulocytosis. He was monitored inpatient for recovery of he neutrophil count. He began to improve after 3 days of monitoring and was discharged. Repeat blood counts 3 months later showed full normalization. Further work-up revealed the etiology of his hyperthyroidism as likely a sub-acute/viral thyroiditis with thyroid I-123 uptake scan at 0.8% at 4, 6, and 24 hours. His hyperthyroidism also resolved over a total of 3 months and his beta-blocker and cholestyramine were discontinued. Discussion This case demonstrates that agranulocytosis is not a dose dependent side effect and can occur with as little as 7 days of therapy that are not even sequentially given. It also may support what very few case reports have demonstrated that even discontinuation of therapy may incite agranulocytosis as a side effect. It helps prescribers inform frequency of surveillance and selection of therapy in hyperthyroidism management. Presentation: No date and time listed

The Prognostic Utility of Lymphocyte-Based Measures and Ratios in Chemotherapy-Induced Febrile Neutropenia Patients following Granulocyte Colony-Stimulating Factor Therapy.

Background and Objectives: Chemotherapy-induced febrile neutropenia is the most widespread oncologic emergency with high morbidity and mortality rates. Herein we present a retrospective risk factor identification study to evaluate the prognostic role of lymphocyte-based measures and ratios in a cohort of chemotherapy-induced febrile neutropenia patients following granulocyte colony-stimulating factor (G-CSF) therapy. Materials and Methods: The electronic medical records at our center were utilized to identify patients with a first attack of chemotherapy-induced febrile neutropenia and were treated accordingly with G-CSF between January 2010 to December 2020. Patients' demographics and disease characteristics along with laboratory tests data were extracted. Prognosis-related indicators were the absolute neutrophil count (ANC) at admission and the following 6 days besides the length of stay and mortality rate. Results: A total of 80 patients were enrolled, which were divided according to the absolute lymphocyte count at admission into two groups, the first includes lymphopenia patients (n = 55) and the other is the non-lymphopenia group (n = 25) with a cutoff point of 700 lymphocytes/μL. Demographics and baseline characteristics were generally insignificant among the two groups but the white blood cell count was higher in the non-lymphopenia group. ANC, neutrophils percentage and ANC difference in reference to admission among the two study groups were totally insignificant. The same insignificant pattern was observed in the length of stay and the mortality rate. Univariate analysis utilizing the ANC difference compared to the admission day as the dependent variable, revealed no predictability role in the first three days of follow up for any of the variables included. However, during the fourth day of follow up, both WBC (OR = 0.261; 95% CI: 0.075, 0.908; p = 0.035) and lymphocyte percentage (OR = 1.074; 95% CI: 1.012, 1.141; p = 0.019) were marginally significant, in which increasing WBC was associated with a reduction in the likelihood of ANC count increase, compared to the lymphocyte percentage which exhibited an increase in the likelihood. In comparison, sequential ANC difference models demonstrated lymphocyte percentage (OR = 0.961; 95% CI: 0.932, 0.991; p = 0.011) and monocyte-to-lymphocyte ratio (OR = 7.436; 95% CI: 1.024, 54.020; p = 0.047) reduction and increment in the enhancement of ANC levels, respectively. The fifth day had WBC (OR = 0.790; 95% CI: 0.675, 0.925; p = 0.003) to be significantly decreasing the likelihood of ANC increment. Conclusions: we were unable to determine any concrete prognostic role of lymphocyte-related measures and ratios. It is plausible that several limitations could have influenced the results obtained, but as far as our analysis is concerned ALC role as a predictive factor for ANC changes remains questionable.

S1190 Therapeutic Effect of Granulocyte Colony-Stimulating Factor Therapy for Acute-on-Chronic Liver Failure: A Meta-Analysis of Randomized Controlled Trials

Introduction: Acute-on-chronic liver failure (ACLF) is a condition characterized by acute decompensation of chronic liver disease, accompanied by the failure of one or more extra-hepatic organs and high short-term mortality. Currently, liver transplantation is the only definitive treatment for ACLF but it is not beneficial to all patients due to limited donors, expensive procedure and high risk of adverse effects, so granulocyte stimulating factor (G-CSF) is considered as an alternative treatment. However, its therapeutic effectiveness is still debaTable, so we aimed to conduct a meta-analysis to evaluate the clinical efficacy of G-CSF In patients with ACLF. Methods: MEDLINE and SCOPUS were queried from inception till June 2022 for randomized controlled trials (RCTs), without any restriction. RCTs evaluating effects of G-CSF on survival rates and occurrence of infection in patients with ACLF were incorporated. The results were reported using a random-effects meta-analysis and the Mantel-Haenszel risk ratio (RR).The Subgroup analysis was done to investigate the influence of study-level factors such as study setting, population and etiology on the outcomes of interest. Results: Thirteen studies (n = 13) were included in our meta-analysis. The total number of participants in our study was 913, and the median study duration was 3 months. Our pooled analysis demonstrates that G-CSF therapy significantly improved survival rates (RR 1.52; 95% CI 1.23 to 1.88; p = 0.0001; Figure) in patients with ACLD. In our subgroup analysis, G-CSF was found to be associated with an improved survival rate in patients with viral hepatitis (RR 1.47; 95% CI 1.27 to 1.69; p < 0.00001). In contrast, results for patients with alcoholic hepatitis were insignificant (RR 1.66; 95% CI 0.88 to 3.16; p< 0.12). Pooled analysis also showed that G-CSF therapy significantly reduces the occurrence rate of infection more than SMT (RR 0.58; 95% CI 0.39 to 0.86; p= 0.006). In the subgroup analysis for viral hepatitis patients, G-CSF therapy was also significantly beneficial in reducing the occurrence rate of infection (RR 0.56; 95% CI 0.35 to 0.89; p=0.01), but in patients with alcoholic hepatitis, results were insignificant (RR 0.55; 95% CI 0.31 to 0.99; p=0.05). Conclusion: Our findings indicate that G-CSF therapy is beneficial in improving survival rates and reducing the risk of infection in patients with ACLF. Hence, it can be used as an alternative treatment for patients with ACLF.Figure 1.: Survival rates in patients with alcoholic hepatitis and viral hepatitis

Granulocyte colony-stimulating factor therapy as a bridging treatment for pediatric decompensated liver cirrhosis prior to liver transplantation: an open-label randomized clinical trial

Background: Decompensated cirrhosis (DC) in children is the main indication of liver transplantation (LT). The lack of access to liver transplantation and impending clinical complications while awaiting transplantation affect the morbidity and mortality in pretransplant patients. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult decompensated cirrhosis as a potential bridging treatment. Our study aimed to identify the effect of G-CSF on pediatric end-stage liver disease (PELD) score, liver function, CD34+ cell mobilization, nutritional status, survival, and short-term side effects in children awaiting LT. Methods: This study was an open-label, randomized controlled trial that included patients with decompensated liver cirrhosis between 3 months and 12 years of age. The intervention group received 12 courses of G-CSF subcutaneous injection (5 μg/kg/day) plus standard medical treatment (SMT) for liver cirrhosis. Results were obtained regarding PELD scores, liver function, CD34+ cell mobilization, changes in leukocyte and neutrophil counts, nutritional status, survival, and side effects within three months. Results: Thirty-five pediatric patients were randomized into the intervention (17 patients) and control (18 patients) groups. During the trial, 14 (82%) in the intervention group completed the treatment. The median ages of the patients in the intervention and control groups were 18 and 14.5 months, respectively. The study's primary outcome identified no statistically significant difference in PELD scores between the intervention and control groups after G-CSF treatment. Liver function tests that showed significant changes in the intervention group compared to the control group were from improvements in alanine aminotransferase (ALT) levels. Other liver function tests, nutritional status, and survival did not. CD34+ cell mobilization was increased in the intervention group compared with the control group, but there was no significant difference. Minor side effects of G-CSF were observed in the intervention group. Conclusion: Multiple doses of G-CSF did not improve the PELD score, nutritional status, and survival after three months but significantly showed temporary improvement in ALT level.

The Treatment of Complementary and Alternative Medicine on Female Infertility Caused by Endometrial Factors.

Recently, with the development of the social economy, the incidence of infertility has increased year by year. With its complex etiology and diversified syndromes, infertility has become one of the most important diseases that plague the physical and mental health of women of childbearing age worldwide. Endometrial factors as an important part affecting female reproductive capacity, due to which induced repeated abortion and multiple uterine cavity operations occur, can destruct endometrium, failing to provide a normal implantation environment for zygote, thus resulting in infertility. Many patients failed to achieve expected results after receiving conventional treatments such as hormone therapy, assisted reproductive technology (ART), granulocyte colony-stimulating factor (G-CSF) therapy, and cell therapy, then turn to complementary and alternative medicine (CAM) therapies for help. Aiming at clarifying the effectiveness and mechanisms of CAM therapy in the treatment of infertility caused by endometrial factors, our paper systematically searched and studied present related literature on the PubMed, CNKI, and other databases, focusing on the aspects of clinical application and mechanism explorations and highlighting the therapeutic effects of Chinese herbal medicine (CHM), acupuncture, and moxibustion on such diseases. Moreover, this paper also introduces the CAM treatments of traditional Chinese medicine (TCM) retention enema, neuromuscular electrical stimulation (NMES), photobiomodulation therapy, dietary intervention, and other measures for infertility caused by endometrial factors, in order to provide a reference for subsequent basic research and clinical work.

Pretreatment hematological parameters as predictors of tumor granulocyte-colony-stimulating factor expression in patients of head-and-neck squamous cell carcinoma.

Tumor secreting granulocyte-colony-stimulating factor (G-CSF) and/or G-CSF therapy has been documented as a poor prognostic factor. Tumor G-CSF study is a relatively costly and sparsely available investigation. Therefore, this study was undertaken to predict tumor G-CSF score from pretreatment hematological parameters (PTHP) in patients of head-and-neck squamous cell carcinoma (HNSCC). This pilot study was performed after institutional ethics committee approval. Consecutive nonmetastatic HNSCC patients of oral cavity, oropharynx, hypopharynx, and larynx registered from February to December 2019 were analyzed. Patients whose PTHP and formalin-fixed-paraffin-embedded tissue were available, were included. PTHP (absolute neutrophil count [ANC], absolute monocyte count [AMC], absolute lymphocyte count [ALC], neutrophil-to-lymphocyte ratio [NLR], and platelet-to-lymphocyte ratio [PLR]) done before any active oncology treatment, were noted. A semiquantitative tumor G-CSF score was calculated. Tumor G-CSF score and PTHP were correlated with clinicopathological factors. Statistical analysis was performed using SYSTAT version 12. Data of 47 eligible patients were analyzed. The median age at presentation was 60 years. The male-to-female ratio was 43:4. The most common head-and-neck subsite was oropharynx (31.92%), and majority of patients presented with Stage IVA disease (51.1%). Higher tumor G-CSF score was significantly associated with a higher T-stage (P = 0.013). Tumor G-CSF score was directly proportional to ANC, AMC, and ALC while it was inversely proportional to NLR and PLR. Regression equations to predict the tumor G-CSF score when PTHP are known, were determined. PTHP can predict the tumor G-CSF score which may guide G-CSF-directed therapy. Future studies with large number of patients are needed to elucidate its clinical use.