Study Of Granulocyte Colony-stimulating Factor Research Articles

A pilot cohort study of granulocyte colony-stimulating factor in the treatment of unresponsive thin endometrium resistant to standard therapies

Is thin endometrium unresponsive to standard treatments expandable by intrauterine perfusion with granulocyte colony-stimulating factor (G-CSF)? This cohort study is supportive of the effectiveness of G-CSF in expanding chronically unresponsive endometria. In a previous small case series, we reported the successful off-label use of G-CSF in four consecutive patients, who had previously failed to expand their endometria beyond 6.9 mm with the use of standard treatments. In a prospective observational cohort pilot study over 18 months, we described 21 consecutive infertile women with endometria <7 mm on the day of hCG administration in their first IVF cycles at our center. All previous cycles using traditional treatments with estradiol, sildenafil citrate (Viagra™) and/or beta-blockers had been unsuccessful. G-CSF (Nupogen™) was administered per intrauterine catheter by slow infusion before noon on the day of hCG administration. If the endometrium had not reached at least a 7-mm within 48h, a second infusion was given following oocyte retrieval. Primary and secondary main outcomes were an increase in endometrial thickness and clinical pregnancy, respectively. Endometrial thickness was assessed by vaginal ultrasound at the most expanded area of the endometrial stripe. This study was uncontrolled, each patient serving as her own control in a prospective evaluation of endometrial thickness. The mean ± SD age of the cohort was 40.5 ± 6.6 years, gravidity was 1.8 ± 2.1 (range 0-7) and parity was 0.4 ± 1.1 (range 0-4); 76.2% of women had, based on age-specific FSH and anti-Müllerian hormone, an objective diagnosis of diminished ovarian reserve and had failed 2.0 ± 2.1 prior IVF cycles elsewhere. With 5.2 ± 1.9 days between G-CSF perfusions and embryo transfers, endometrial thickness increased from 6.4 ± 1.4 to 9.3 ± 2.1 mm (P < 0.001). The Δ in change was 2.9 ± 2.0 mm, and did not vary between conception and non-conception cycles. A 19.1% ongoing clinical pregnancy rate was observed, excluding one ectopic pregnancy. Small sample size (but a highly selected patient population) in an uncontrolled cohort study and in unselected first IVF cycles at our center. This pilot study supports the utility of G-CSF in the treatment of chronically thin endometrium and suggests that such treatment will, in very adversely affected patients, result in low but very reasonable clinical pregnancy rates. This work was supported by the Foundation for Reproductive Medicine, New York, New York, USA, a not-for-profit research foundation and intramural grants from the Center for Human Reproduction (CHR)-New York. N.G. and D.H.B. are members of the board of the Foundation for Reproductive Medicine. N.G. is owner of CHR-New York, where the study was conducted. N.G. and D.H.B. have been recipients of research awards, travel grants and speaker honoraria from various pharmaceutical and medical device companies. None of these companies was, however, in any way associated with the materials and the manuscript presented here. N.G. and D.H.B. are listed as co-inventors on a number of awarded and still pending U.S. patents, none related to the materials presented here. N.G. is on the board of a medically related company, not in any way associated with the data presented here.

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.

The End of Granulocyte Colony-Stimulating Factor in Acute Myocardial Infarction?

“Perfect as the wing of a bird may be, it will never enable the bird to fly if unsupported by the air. Facts are the air of science. Without them a man of science can never rise.” — —Ivan Pavlov Facts must be sought from the rigorous application of scientific method. Indeed, the hardest questions sometimes require the hardest methods. Having a tool that can answer the questions with the minimum number of side effects in the minimum number of patients must be the desire of all clinical investigators who wish to generate new facts and contribute to the pool of knowledge. Progress in cell therapy for cardiovascular disease has been hindered at both the preclinical and clinical stages, perhaps because the appropriate tools to address the pertinent questions have not been used. In this context, magnetic resonance imaging (MRI) has, by necessity, rapidly evolved as the ideal tool for surrogate end-point measurements in early-phase clinical trials. In this issue of Circulation , Ripa and colleagues1 have elegantly demonstrated the utility and maturation of this technology in their study of granulocyte colony-stimulating factor (G-CSF) as an adjunctive therapy to mechanical reperfusion after myocardial infarction. Article p 1983 Cardiovascular cell transplantation and cytokine mobilization originally began in clinical trials with the explicit goal of myocardial regeneration,2,3 but more recently, the emphasis has been focused on “remodeling attenuation” therapy, in which the presumed mechanism has shifted from the “replacement” capacity of transplanted cells to their “paracrine” effects.4 This thesis becomes more convincing given the lack of cardiomyogenic transdifferentiation demonstrated by adult hematopoietic stem cells.5 Despite the indistinct mechanism, the early-phase, nonrandomized clinical studies of G-CSF given after myocardial infarction demonstrated provocatively the potential efficacy of G-SCF administered as sole therapy.6,7 The study presented in this issue of …

An Open-Label Pilot Study of Granulocyte Colony-Stimulating Factor for the Treatment of Severe Endoscopic Postoperative Recurrence in Crohn’s Disease

Background/Aim: Recombinant human granulocyte colony-stimulating factor (rhG-CSF) promoted healing of Crohn’s disease (CD)-like intestinal lesions in chronic granulomatous disease and glycogen storage disease Ib, both characterized by defective neutrophil functions. We performed a prospective, open-label pilot study with rhG-CSF for the treatment of CD. Patients andMethods: Five patients with clinically inactive CD, but with severe endoscopic ileitis within 1 year after intestinal resection and ileocolonic anastomosis, received 300 µg of rhG-CSF (Filgrastim; Neupogen^®) subcutaneously, three times weekly for a total of 12 weeks. Safety was evaluated by assessment of clinical and laboratory data and disease activity. The primary parameter of efficacy was complete mucosal healing, as defined by the Rutgeerts score. Anti-inflammatory mediators were repeatedly measured during treatment. Results: All patients completed the protocol in clinical remission. In 1 subject transient headache resolved after halving the rhG-CSF dosage. Complete mucosal healing was observed in 2 patients: in 1 patient after 12 weeks of therapy and in 1 patient 9 months after treatment cessation. In a single patient, closure of an anovaginal and of a perianal fistula was noted. Neutrophil counts and interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor p55 and p75 levels were found to be increased during drug administration. Conclusion: rhG-CSF seems to be safe, well tolerated, and might provide efficacy in CD.

Regulation of granulopoiesis: lessons from leukocyte adhesion deficiency

The mechanisms that regulate granulopoiesis, in particular, stress (or “emergency”) granulopoiesis, are incompletely understood. Studies of granulocyte colony-stimulating factor (G-CSF) or G-CSF receptor–deficient mice provide strong evidence that G-CSF is the principal hematopoietic cytokine

A Double-Blind Controlled Study of Granulocyte Colony-Stimulating Factor Started Two Days Before Induction Chemotherapy in Refractory Acute Myeloid Leukemia

Abstract We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G- CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P &lt; .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2- week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G- CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group [see comments

We conducted a prospective, double-blind controlled study to determine the efficacy of a recombinant granulocyte colony-stimulating factor (G-CSF, 200 microgram/m2) starting daily from 2 days before an induction therapy until neutrophils recovered to above 1,500/microL or until 35 days after the therapy in 58 patients with relapsed or refractory acute myeloid leukemia (AML). Twenty-eight patients in the G-CSF group showed significantly faster recovery of neutrophils (P < .001) than 30 patients in the placebo group. The incidence of febrile episodes and of documented infections was almost the same in both groups. However, among 39 patients who did not show any infectious episodes during the 2-week period after the start of chemotherapy, the incidence of documented infections after the third week tended to be lower in the G-CSF group, but not statistically significantly. There was no evidence that G-CSF stimulated the growth of AML cells in the bone marrow during the 2-day period before the chemotherapy, nor that G-CSF accelerated the regrowth of AML cells during the 5-week period after the therapy. Fifty percent of patients in the G-CSF group and 37% in the placebo group had complete remission (CR). Although the rate was higher in the G-CSF group, the difference was not statistically significant (P = .306). There was no difference between the two groups in event-free survival of all patients and in disease-free survival of patients who had achieved CR.

Phase I study of granulocyte colony-stimulating factor in patients with transitional cell carcinoma of the urothelium.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was administered at a dose of 1-60 micrograms/kg of body weight to 22 patients with transitional cell carcinoma before chemotherapy as part of a Phase I/II study. In all patients, a specific dose-dependent increase in the absolute neutrophil count (ANC) of 1.8-12 fold was seen. In addition, this augmentation in the ANC was accompanied by an increase in leukocyte alkaline phosphatase, a marker of secondary granule formation. In six of eight patients analyzed, an increase in bone marrow myeloid to erythroid cell ratio was seen. Day 14 peripheral blood cell derived colony forming unit granulocyte macrophage were also increased by day 6 of rhG-CSF treatment. Circulating levels of eosinophils and basophils were unchanged; however, a 10-fold increase in monocytes was observed in patients treated at the highest doses. There was also a small increase in CD3+ lymphocytes that was not dose dependent. Hemoglobin, hematocrit, and platelet count remained near baseline throughout the period of rhG-CSF administration. These findings demonstrate that rhG-CSF is a potent stimulus for normal neutrophil proliferation and maturation.