Granulocyte Colony-stimulating Factor Therapy In Patients Research Articles

Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in a Tertiary Treatment Care Center of Bangladesh

ABSTRACT Introduction Decompensated cirrhosis is associated with significantly high mortality resulting from hepatic failure, and liver transplantation seems to be the only viable indication for its management. The objective of this study is to assess if granulocyte colony-stimulating factor (G-CSF), a stimulatory of stem cell in vivo, may be of any benefit for patients with decompensated cirrhosis of liver. Materials and methods Seventeen consecutive patients with decompensated cirrhosis of liver were recruited in this prospective study. They received injection of G-CSF (30 IU) over a period of 6 weeks (12 injections) in addition to standard of care. Results Patients were followed up at the end of treatment and at 12 weeks of treatment. Treatment was well tolerated, and no significant adverse event was recorded in any patient. Fifteen out of 17 (88%) patients were alive at last follow-up. Although serum bilirubin, albumin, and prothrombin time improved in some patients, statistically significant improvement of Child–Pugh score could not be documented. Conclusion The study establishes the safety of G-CSF therapy in patients with decompensated cirrhosis of liver. Besides, such therapy may also have survival benefit, although long-term follow-up is needed to assess its real utility in clinical perspectives. How to cite this article Al Mahtab M, Alam SMN, Moben AL, Raihan R, Alam MA, Rahim MA, Uddin MH, Akbar SMF. Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in a Tertiary Treatment Care Center of Bangladesh. Euroasian J Hepato-Gastroenterol 2017;7(1):113-115. Source of support The study was partially supported by a grant from Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in a Tertiary Treatment Care Center of Bangladesh.

Introduction:Decompensated cirrhosis is associated with significantly high mortality resulting from hepatic failure, and liver transplantation seems to be the only viable indication for its management. The objective of this study is to assess if granulocyte colony-stimulating factor (G-CSF), a stimulatory of stem cell in vivo, may be of any benefit for patients with decompensated cirrhosis of liver.Materials and methods:Seventeen consecutive patients with decompensated cirrhosis of liver were recruited in this prospective study. They received injection of G-CSF (30 IU) over a period of 6 weeks (12 injections) in addition to standard of care.Results:Patients were followed up at the end of treatment and at 12 weeks of treatment. Treatment was well tolerated, and no significant adverse event was recorded in any patient. Fifteen out of 17 (88%) patients were alive at last follow-up. Although serum bilirubin, albumin, and prothrombin time improved in some patients, statistically significant improvement of Child-Pugh score could not be documented.Conclusion:The study establishes the safety of G-CSF therapy in patients with decompensated cirrhosis of liver. Besides, such therapy may also have survival benefit, although long-term follow-up is needed to assess its real utility in clinical perspectives.How to cite this article: Al Mahtab M, Alam SMN, Moben AL, Raihan R, Alam MA, Rahim MA, Uddin MH, Akbar SMF. Therapy Targeting Stem Cell in Patients with Decompensated Cirrhosis of Liver in a Tertiary Treatment Care Center of Bangladesh. Euroasian J Hepato-Gastroenterol 2017;7(1):113-115.

Granulocyte colony stimulating factor therapy for acute myocardial infarction

Acute myocardial infarction (AMI) is the leading cause of death in developed countries, and current treatment modalities have failed to regenerate the dead myocardium resulting from the ischemic damage. Stem cells have the potential to regenerate the damaged myocardium. These cells can be mobilized from the bone marrow by factors such as granulocyte colony stimulating factor (G-CSF). To assess the effects of stem cell mobilization following granulocyte colony stimulating factor therapy in patients with acute myocardial infarction. We searched CENTRAL (The Cochrane Library Issue 4, 2010), MEDLINE (1950 to November week 3, 2010), EMBASE (1980 to 2010 week 48), BIOSIS Previews (1969 to 30 November 2010), ISI Science Citation Index Expanded (1970 to 4 December 2010) and ISI Conference Proceedings Citation Index - Science (1990 to 4 December 2010). We also checked reference lists of articles. We included randomized controlled trials including participants with a clinical diagnosis of AMI who were randomly allocated to the subcutaneous administration of G-CSF through a daily dose of 2.5, 5 or 10 microgram/kg for four to six days or placebo. No age or other restrictions were applied for the selection of patients. Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data regarding the clinical efficacy and adverse outcomes. Disagreements were resolved by the third author. We included seven trials reported in 30 references in the review (354 participants). In all trials, G-CSF was compared with placebo preparations. Dosage of G-CSF varied among studies, ranging from 2.5 to 10 microgram/kg/day. Regarding overall risk of bias, data regarding the generation of randomization sequence and incomplete outcome data were at a low risk of bias; however, data regarding binding of personnel were not conclusive. The rate of mortality was not different between the two groups (RR 0.64, 95% CI 0.15 to 2.80, P = 0.55). Regarding safety, the limited amount of evidence is inadequate to reach any conclusions regarding the safety of G-CSF therapy. Moreover, the results did not show any beneficial effects of G-CSF in patients with AMI regarding left ventricular function parameters, including left ventricular ejection fraction (RR 3.41, 95% CI -0.61 to 7.44, P = 0.1), end systolic volume (RR -1.35, 95% CI -4.68 to 1.99, P = 0.43) and end diastolic volume (RR -4.08, 95% CI -8.28 to 0.12, P = 0.06). It should also be noted that the study was limited since the trials included lacked long enough follow up durations. Limited evidence from small trials suggested a lack of benefit of G-CSF therapy in patients with AMI. Since data of the risk of bias regarding blinding of personnel were not conclusive, larger RCTs with appropriate power calculations and longer follow up durations are required in order to address current uncertainties regarding the clinical efficacy and therapy-related adverse events of G-CSF treatment.

Mobilization of Stem Cells Using G-CSF for Acute Ischemic Stroke: A Randomized Controlled, Pilot Study.

Background. There is emerging evidence to support the use of granulocyte colony-stimulating factor (G-CSF) therapy in patients with acute ischemic stroke. Aims. To explore feasibility, safety, and preliminary efficacy of G-CSF therapy in patients with acute ischemic stroke. Patients and Method. In randomized study, 10 patients with acute ischemic stroke were recruited in 1 : 1 ratio to receive 10 μg/kg G-CSF treatment subcutaneously daily for five days with conventional care or conventional treatment alone. Efficacy outcome measures were assessed at baseline, one month, and after six months of treatment included Barthel Index (BI), National Institute of Health Stroke Scale, and modified Rankin Scale. Results. One patient in G-CSF therapy arm died due to raised intracranial pressure. No severe adverse effects were seen in rest of patients receiving G-CSF therapy arm or control arm. No statistically significant difference between intervention and control was observed in any of the scores though a trend of higher improvement of BI score is seen in the intervention group. Conclusion. Although this study did not have power to examine efficacy, it provides preliminary evidence of potential safety, feasibility, and tolerability of G-CSF therapy. Further studies need to be done on a large sample to confirm the results.

Granulocyte colony-stimulating factor therapy for cardiac repair after acute myocardial infarction: A systematic review and meta-analysis of randomized controlled trials

Small clinical studies of granulocyte colony-stimulating factor (G-CSF) therapy for cardiac repair after acute myocardial infarction (MI) have yielded divergent results. The effect of G-CSF therapy on left ventricular (LV) function and structure in these patients remains unclear. We searched MEDLINE, EMBASE, Science Citation Index, CINAHL, and the Cochrane CENTRAL database of controlled clinical trials (July 2007) for randomized controlled trials of G-CSF therapy in patients with acute MI. We conducted a fixed-effects meta-analysis across 8 eligible studies (n = 385 patients). Compared with controls, G-CSF therapy increased LV ejection fraction (EF) by 1.09%, increased LV scar size by 0.22%, decreased LV end-diastolic volume by 4.26 mL, and decreased LV end-systolic volume by 2.50 mL. None of these effects were statistically significant. The risk of death, recurrent MI, and in-stent restenosis was similar in G-CSF-treated patients and controls. Subgroup analysis revealed a modest but statistically significant increase in EF (4.73%, P < .0001) with G-CSF therapy in studies that enrolled patients with mean EF <50% at baseline. Subgroup analysis also showed a significant increase in EF (4.65%, P < .0001) when G-CSF was administered relatively early (< or =37 hours) after the acute event. Granulocyte colony-stimulating factor therapy in unselected patients with acute MI appears safe but does not provide an overall benefit. Subgroup analyses suggest that G-CSF therapy may be salutary in acute MI patients with LV dysfunction and when started early. Larger randomized studies may be conducted to evaluate the potential benefits of early G-CSF therapy in acute MI patients with LV dysfunction.

G-CSF therapy for acute myocardial infarction: Studies of animal experiments give valuable hints to clinical trials

Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic cytokine that promotes proliferation and differentiation of neutrophil progenitors. Clinically, hematopoietic stem cells mobilized by G-CSF are widely used for transplantation. G-CSF has been reported to mobilize bone marrow stem cells and regenerate infarcted hearts of mice. Besides mobilization, G-CSF has activated various signaling pathways such as Akt and Janus family kinase-2/signal transducer and activator of transcription-3 through G-CSF receptors in cardiac myocytes and has markedly prevented left ventricular remodeling after acute myocardial infarction by decreasing cardiomyocyte death and increasing the number of vessels. Although several clinical trials have been performed, the efficacy of G-CSF therapy in patients with acute myocardial infarction is still controversial.

G-CSF therapy for acute myocardial infarction

Granulocyte-colony-stimulating factor (G-CSF) has recently been shown to have various effects besides promoting the proliferation and differentiation of myeloid progenitor cells, including the mobilization of bone marrow stem cells and the regeneration infarcted hearts in mice. Recent animal studies have also revealed that G-CSF activates multiple signaling pathways, such as Akt and also the Janus family kinase-2 and signal transducer and activation of transcription-3 (Jak2-STAT3) pathway, in cardiac myocytes. It prevents left ventricular remodeling after myocardial infarction by decreasing cardiomyocyte death and by increasing the number of blood vessels, suggesting the importance of direct actions of G-CSF on the myocardium rather than through mobilization and differentiation of stem cells. Several clinical trials have been performed to study the efficacy of G-CSF therapy in patients with acute myocardial infarction but the results remain controversial because the protocols followed varied between the trials.

Stem Cell Mobilization by Granulocyte Colony-Stimulating Factor in Patients With Acute Myocardial Infarction&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;

Experimental studies and early phase clinical trials suggest that transplantation of blood-derived or bone marrow-derived stem cells may improve cardiac regeneration and neovascularization after acute myocardial infarction. Granulocyte colony-stimulating factor (G-CSF) induces mobilization of bone marrow stem cells. To assess the value of stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction. Randomized, double-blind, placebo-controlled trial of patients diagnosed with ST-segment elevation acute myocardial infarction who had successful reperfusion by percutaneous coronary intervention within 12 hours after onset of symptoms in Germany between February 24, 2004, and February 2, 2005. Patients were randomly assigned to receive subcutaneously either a daily dose of 10 microg/kg of G-CSF or placebo for 5 days. The primary end point was reduction of left ventricular infarct size according to technetium Tc 99m sestamibi scintigraphy performed at baseline and at 4 to 6 months after randomization. Secondary end points included improvement of left ventricular ejection fraction measured by magnetic resonance imaging and the incidence of angiographic restenosis. Of the 114 patients, 56 were assigned to receive treatment with G-CSF and 58 were assigned to receive placebo. Treatment with G-CSF produced a significant mobilization of stem cells. Between baseline and follow-up, left ventricular infarct size according to scintigraphy was reduced by a mean (SD) of 6.2% (9.1%) in the G-CSF group and 4.9% (8.9%) in the placebo group (P = .56) and left ventricular ejection fraction was improved by 0.5% (3.8%) in the G-CSF group and 2.0% (4.9%) in the placebo group (P = .14). Angiographic restenosis occurred in 19 (35.2%) of 54 patients in the G-CSF group and in 17 (30.9%) of 55 patients in the placebo group (P = .79). The most common adverse event among patients assigned to G-CSF was mild to moderate bone pain and muscle discomfort. Stem cell mobilization by G-CSF therapy in patients with acute myocardial infarction and successful mechanical reperfusion has no influence on infarct size, left ventricular function, or coronary restenosis. ClinicalTrials.gov Identifier: NCT00126100.