Safety Of Granulocyte Colony-stimulating Factor Research Articles

Comparison of two autologous hematopoietic stem cell mobilization strategies in patients with multiple myeloma: CE plus G-CSF versus G-CSF only: A single-center retrospective analysis.

Despite recent advances in the treatment of multiple myeloma, high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (ASCT) remains an essential therapeutic keystone. As for the stem cell mobilization procedure, different regimens have been established, usually consisting of a cycle of chemotherapy followed by application of granulocyte-colony stimulating factor (G-CSF), although febrile neutropenia is a common complication. Following national guidelines, our institution decided to primarily use G-CSF only mobilization during the COVID-19 pandemic to minimize the patients' risk of infection and to reduce the burden on the health system. In this retrospective single-center analysis, the efficacy and safety of G-CSF only mobilization was evaluated and compared to a historic control cohort undergoing chemotherapy-based mobilization by cyclophosphamide and etoposide (CE) plus G-CSF. Although G-CSF only was associated with a higher need for plerixafor administration (p < .0001) and a higher number of apheresis sessions per patient (p = .0002), we were able to collect the target dose of hematopoietic stem cells in the majority of our patients. CE mobilization achieved higher hematopoietic stem cell yields (p = .0015) and shorter apheresis sessions (p < .0001) yet was accompanied by an increased risk of febrile neutropenia (p < .0001). There was no difference in engraftment after ASCT. G-CSF only mobilization is a useful option in selected patients with comorbidities and an increased risk of serious infections, especially in the wintertime or in future pandemics.

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.

P1358: WILL COVID-19 PANDEMIC CHANGE MOBILIZATION STRATEGY OF HEMATOPOIETIC STEM CELLS IN MULTIPLE MYELOMA PATIENTS FOR THE BETTER?

Background: Autologous hematopoietic stem cell transplantation (ASCT) is the current standard of care for younger patients (pts) with multiple myeloma (MM), improving overall survival (OS) and progression free survival (PFS). According to EBMT, use of chemotherapy, typically cyclophosphamide (Cy), in combination with granulocyte colony-stimulating factor (G-CSF) is the preferred strategy for hematopoietic stem cell (HSC) mobilization to peripheral blood (PB). However, major disadvantages are therapy-related toxicity and higher mobilization failure. Plerixafor plus G-CSF has been shown to be superior to G-CSF alone, leading to higher CD34+ yields in fewer apheresis sessions; however there are few data in comparison to chemomobilization. Since the beginning of COVID-19 pandemic, our center adopted G-CSF ± Plerixafor as initial strategy to mobilize HSC in MM pts. Aims: To evaluate the efficacy, length of hospitalization and safety of G-CSF ± Plerixafor mobilization of HSC in MM pts, compared to chemomobilization. Methods: We performed a retrospective study of MM pts submitted to mobilization and 1st ASCT between 2018 and 2021. Pts who underwent mobilization with Cy (1.5 g/m2) plus pegylated G-CSF were included in group A; pts who received G-CSF ± Plerixafor were included in group B. Group B only received Plerixafor if they presented PB CD34+ cells < 15/mL on day 4 of mobilization with G-CSF. Results: We identified a total of 126 pts, excluded 4 (2 under hemodialysis and 2 receiving different protocols) and included 122 pts, 83 (68%) in group A and 39 (32%) in group B. Demographic characteristics and disease stage (ISS and R-ISS) were similar between the groups, presenting a male predominance (n=73, 60%) and a median age of 61 years. Since frontline protocol in MM changed recently, induction therapy in group A and B was, respectively, VCD 60 vs 26%; VRD 30 vs 75%; VTD 10 vs 0% (P<0.001). No differences were observed in pre-ASCT quality of responses (89.2 vs 89.7% ≥VGPR; P=0.532). The impact of apheresis in terms of length of hospitalization (4 vs 2 days, P<0.001) and median time from the 4th day of mobilization with G-CSF until first apheresis was lower in group B; 2 vs 1 days, P<0.001). There was no difference in the number of apheresis sessions (1 vs 1; P=0.260). The volume of DMSO was higher in group B (22 vs 30 mL, P=0.001). In group B, 16 (41%) pts did not need Plerixafor and there were no differences in length of hospitalization or the number of apheresis sessions compared with those who received Plerixafor. Mobilization failure was only seen in group A, (n=14, 17%, P=0.006). Poor mobilizers were remobilized with G-CSF + Plerixafor and presented longer hospitalization (4 vs 2 days, P=0.001) and number of apheresis sessions (2 vs 1 days, P=0.001) when compared to group B. During mobilization, grade ≥3 complications were observed in 8.4% (n=3) in group A, being febrile neutropenia the most frequent; mobilization was interrupted in 2 pts. All pts presented neutrophil and platelet engraftment and there was no difference in time of engraftment after ASCT between groups A and B (12 days in both, P=0.711). No differences were observed in PFS (74.5 vs 40 months, HR 0.8[0.2-2.9], P=0.782) or OS (82.6 vs NR, HR 1.1[0.2-6.0], P=0.839) between groups. Summary/Conclusion: The mobilization protocol changed, due to COVID-19 pandemic, from chemomobilization to G-CSF ± Plerixafor and resulted in less hospital resource utilization and less febrile neutropenia, without compromising ASCT success. Unlike prior reports, number of apheresis sessions after mobilization with G-CSF alone was similar to G-CSF + Plerixafor.

Don't Go Breakin’ My Heart: Lack of Association between Granulocyte Colony Stimulating Factor and Development of Acute Cellular Rejection

Purpose Neutropenia commonly occurs after heart transplantation (HT) and granulocyte colony-stimulating factor (GCSF) may be used for treatment of neutropenia in this setting. Published data is lacking on the incidence and etiology of neutropenia, and the safety of GCSF with respect to subsequent risk of acute rejection. Methods This was a retrospective study in adult HT recipients from 2012-2018 at a single institution. All patients who received at least one dose of GCSF were identified and compared with patients without a history of therapy in the first year of HT. Patients were evaluated for acute cellular rejection (ACR) ≥2R within 3 and 12 months after GCSF. This was compared with the incidence of ACR in the non-GCSF group starting 4.5 months after HT (as the mean time to first neutropenic episode was 142 days in the GCSF group). Categorical variables were compared using the chi-square test. Results Of the 211 recipients included in the overall cohort, 71.1% were male, 58.3% were Caucasian, and 24.2% had ischemic cardiomyopathy. Mean age was 52.5 ± 12.1 years. In this cohort, 71 (33.6%) developed 136 episodes of neutropenia (mean 1.9 episodes/patient) requiring at least one dose of GCSF. Moderate (ANC 501-999/mcL) and severe (ANC ≤500/mcL) neutropenia was seen in 41.9% and 25% of cases, respectively. 78.9% of neutropenic cases were thought to be medication related based on chart review. Nearly all patients were induced with ATG (94.3%) and 24.6% were primary mismatch for cytomegalovirus. Each cycle of GCSF required on average 3.4 doses, with a mean total dose of 18.8 mcg/kg. The mean ANC nadir and peak was 850 ± 580/mcL and 7,520 ± 5,210/mcL, respectively. The mean time from HT to first neutropenic episode was 142 ± 100 days. Incidence of ACR ≥2R within the first 3 and 12 months was not significantly different between the GCSF (3 mo.: 9.9% and 12 mo.: 14.1%) and non-GCSF groups (3 mo.: 4.3% and 12 mo.: 18.6%) (p>0.05). Conclusion In this study, GCSF treated neutropenia occurred in one-third of patients within the first year after HT. GCSF does not appear to increase subsequent risk of ACR within the first year after GCSF administration.

BBCIC Research Network Analysis of First-Cycle Prophylactic G-CSF Use in Patients Treated With High-Neutropenia Risk Chemotherapy.

Chemotherapy-induced febrile neutropenia (FN) is prevented or minimized with granulocyte colony-stimulating factors (G-CSFs). Several G-CSF biosimilars are approved in the United States. The Biologics and Biosimilars Collective Intelligence Consortium (BBCIC) is a nonprofit initiative whose objective is to provide scientific evidence on real-world use and comparative safety and effectiveness of biologics and biosimilars using the BBCIC distributed research network (DRN). We describe real-world G-CSF use in patients with breast or lung cancer receiving first-cycle chemotherapy associated with high FN risk. We assessed hospitalizations for FN, availability of absolute neutrophil counts, and G-CSF-induced adverse events to inform future observational comparative effectiveness studies of G-CSF reference products and their biosimilars. A descriptive analysis of 5 participating national health insurance plans was conducted within the BBCIC DRN. A total of 57,725 patients who received at least one G-CSF dose were included. Most (92.5%) patients received pegfilgrastim. FN hospitalization rates were evaluated by narrow (<0.5%), intermediate (1.91%), and broad (2.99%) definitions. Anaphylaxis and hyperleukocytosis were identified in 1.15% and 2.28% of patients, respectively. This analysis provides real-world evidence extracted from a large, readily available database of diverse patients, characterizing G-CSF reference product use to inform the feasibility of future observational comparative safety and effectiveness analyses of G-CSF biosimilars. We showed that the rates of FN and adverse events in our research network are consistent with those reported by previous small studies. Readily available BBCIC DRN data can be used to assess G-CSF use with the incidence of FN hospitalizations. Insufficient laboratory result data were available to report absolute neutrophil counts; however, other safety data are available for assessment that provide valuable baseline data regarding the effectiveness and safety of G-CSFs in preparation for comparative effectiveness studies of reference G-CSFs and their biosimilars.

Safety of G-CSF with concurrent chemo-radiotherapy in limited-stage small cell lung cancer - Secondary analysis of the randomised phase 3 CONVERT trial

ObjectivesThe use of granulocyte colony-stimulating factors (G-CSF) during concurrent chemo-radiotherapy (cCTRT) for small cell lung cancer is not recommended by the American Society of Clinical Oncology due to safety concerns. This secondary analysis explored the safety and the role of prophylactic G-CSF (proG-CSF) in the delivery of cCTRT. Material and methodsSecondary analysis of 487 patients treated as per protocol on the phase 3 CONVERT trial which randomized patients between once-daily RT or twice-daily. Results180 of 487 eligible patients (37 %) received proG-CSF, 60 (33 %) as primary prophylaxis and 120 (67 %) as secondary prophylaxis following myelotoxic events. The regimen incidence of febrile neutropenia (FN) was 22 %. Its incidence in the proG-CSF group reduced significantly when proG-CSF was administered (22 % vs 10 %; OR 0.4; 95 %CI 0.2−0.7; p = 0.002). The rate of blood transfusion was higher in the proG-CSF group (51 % vs 31 %; OR 2.4; 95 %CI 1.6–3.5; p < 0.001). The incidence of severe thrombocytopenia was also higher is this group (28 % vs 15 %; OR 2.2; 95 %CI 1.4–3.5; p = 0.001). But this was significantly higher in those on secondary vs primary prophylaxis (34 % vs 15 %; OR 2.9; 95 %CI 1.3–7.4 p = 0.009) No differences observed in RT-related toxicity, treatment-related mortality or any survival outcomes. The optimal dose intensity (85 % or higher) of cisplatin was achieved in more patients within the proG-CSF group (75 % vs 67 %; OR 1.5; 95 %CI 0.9–2.3; p = 0.056). ConclusionThere was no evidence that G-CSF directly caused myelotoxicity, instead most patients started G-CSF due to higher myelotoxicity risk. G-CSF maintained the planned dose intensity and there was no detrimental effect on survival. G-CSF may be considered as a supportive measure in this setting.

Granulocyte-colony stimulating factor administration for subfertile women undergoing assisted reproduction.

Granulocyte-colony stimulating factor (G-CSF) seems to play an important role in the process of embryo implantation and continuation of pregnancy. It has been used during in vitro fertilisation (IVF) treatment for subfertile women with chronically thin endometrium and those with previous multiple IVF failures. It is currently unknown whether G-CSF is effective in improving results following assisted reproductive technology (ART). To evaluate the effectiveness and safety of G-CSF in women undergoing ART. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform in February 2019. We searched reference lists of relevant articles and handsearched relevant conference proceedings. Randomised controlled trials (RCTs) comparing G-CSF administration versus no treatment or placebo in subfertile women undergoing IVF treatment. Two review authors independently screened studies, extracted data, and assessed risk of bias. The primary outcomes were live-birth rate and miscarriage rate following G-CSF administration. We have reported ongoing pregnancy rate in cases where studies did not report live birth but reported ongoing pregnancy. Secondary outcomes were clinical pregnancy rate, multiple pregnancy rate, adverse events, ectopic pregnancy rate, small for gestational age at birth, abnormally adherent placenta, and congenital anomaly rate. We analysed data using risk ratio (RR), Peto odds ratio and a fixed-effect model. We assessed the quality of the evidence using the GRADE criteria. We included 15 trials involving 622 women who received G-CSF and 631 women who received placebo or no additional treatment during IVF. The main limitations in the quality of the evidence were inadequate reporting of study methods and high risk of performance bias due to lack of blinding. We assessed only two of the 15 included trials as at a low risk of bias. None of the trials reported the primary effectiveness outcome of live-birth rate. We are uncertain whether G-CSF administration improves ongoing pregnancy rate compared to control in subfertile women undergoing ART (RR 1.42, 95% confidence interval (CI) 0.83 to 2.42; 2 RCTs; participants = 263; I² = 0%; very low-quality evidence). For a typical clinic with 14% ongoing pregnancy rate, G-CSF administration would be expected to result in ongoing pregnancy rates between 12% and 35%. We are uncertain whether G-CSF administration reduces miscarriage rate (Peto odds ratio 0.55, 95% CI 0.17 to 1.83; 3 RCTs; participants = 391; I² = 0%; very low-quality evidence) compared to the control group in subfertile women undergoing ART. We are uncertain whether G-CSF administration improves overall clinical pregnancy rate compared to control in subfertile women undergoing ART (RR 1.63, 95% CI 1.32 to 2.01; 14 RCTs; participants = 1253; I² = 13%; very low-quality evidence). For a typical clinic with 17% clinical pregnancy rate, G-CSF administration would be expected to result in clinical pregnancy rates between 23% and 35%. In the unselected IVF population, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.11, 95% CI 0.77 to 1.60; 3 RCTs; participants = 404; I² = 0%; low-quality evidence). G-CSF administration may improve clinical pregnancy rate in women with two or more previous IVF failures compared to the control group (RR 2.11, 95% CI 1.56 to 2.85; 7 RCTs; participants = 643; I² = 0%; low-quality evidence). In subfertile women with thin endometrium undergoing ART, we are uncertain whether G-CSF administration improves clinical pregnancy rate compared to the control group (RR 1.58, 95% CI 0.95 to 2.63; 4 RCTs; participants = 206; I² = 30%; low-quality evidence). No study reported on multiple pregnancy rate. Only four trials reported adverse events as an outcome, and none of them reported any major adverse events following either G-CSF administration or placebo/no treatment. In subfertile women undergoing ART, we are uncertain whether the administration of G-CSF improves ongoing pregnancy or overall clinical pregnancy rates or reduces miscarriage rate compared to no treatment or placebo, whether in all women or those with thin endometrium, based on very low-quality evidence. Low-quality evidence suggests that G-CSF administration may improve clinical pregnancy rate in women with two or more IVF failures, but the included studies had unclear allocation concealment or were at high risk of performance bias.

Efficacy of Granulocyte Colony‐stimulating Factor in the Management of Steroid‐Nonresponsive Severe Alcoholic Hepatitis: A Double‐Blind Randomized Controlled Trial

Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300 μg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G-CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28-day mortality was comparable between the groups (21.4%, G-CSF; 28.6%, placebo; P = 0.69). At 90 days, in the G-CSF but not in the placebo group, the Model for End-Stage Liver Disease reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P = 0.002) and Maddrey's discriminant function from 74.8 ± 22.8 to 57.4 ± 31 (P = 0.26). Infections were less common (28% versus 71%; P < 0.001) with lower 90-day mortality (35.7% versus 71.4%; P = 0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio, 0.37; SD, 0.14-0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7-10.3; P = 0.002) predicted day-90 outcomes in steroid nonresponsive SAH. Patients tolerated G-CSF without any major adverse events. Conclusion: Approximately one-quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G-CSF is safe and helps to reduce the disease severity and 90-day mortality in these patients.

Outcome From a Randomized Controlled Clinical Trial - Improvement of Peripheral Arterial Disease by Granulocyte Colony-Stimulating Factor-Mobilized Autologous Peripheral-Blood-Mononuclear Cell Transplantation (IMPACT).

The clinical usefulness of peripheral blood (PB) mononuclear cell (MNC) transplantation in patients with peripheral arterial disease (PAD), especially in those with mild-to-moderate severity, has not been fully clarified.Methods and Results:A randomized clinical trial was conducted to evaluate the efficacy and safety of granulocyte colony-stimulating factor (G-CSF)-mobilized PBMNC transplantation in patients with PAD (Fontaine stage II-IV and Rutherford category 1-5) caused by arteriosclerosis obliterans or Buerger's disease. The primary endpoint was progression-free survival (PFS). In total, 107 subjects were enrolled. At baseline, Fontaine stage was II/III in 82 patients and IV in 21, and 54 patients were on hemodialysis. A total of 50 patients had intramuscular transplantation of PBMNC combined with standard of care (SOC) (cell therapy group), and 53 received SOC only (control group). PFS tended to be improved in the cell therapy group than in the control group (P=0.07). PFS in Fontaine stage II/III subgroup was significantly better in the cell therapy group than in the control group. Cell therapy-related adverse events were transient and not serious. In this first randomized, large-scale clinical trial of G-CSF-mobilized PBMNC transplantation, the cell therapy was tolerated by a variety of PAD patients. The PBMNC therapy was significantly effective for inhibiting disease progression in mild-to-moderate PAD.

Abstract P3-14-05: Safety of granulocyte colony-stimulating factors and their biosimilars: A meta-analysis of randomized clinical trials in breast cancer patients receiving cytotoxic chemotherapy

Abstract Background: Neutropenia is a common adverse event reported in cancer patients undergoing cytotoxic chemotherapy. Granulocyte colony-stimulating factors (G-CSFs) such as filgrastim and pegfilgrastim are widely used to prevent neutropenia. Several biosimilars of G-CSF are now available. Biosimilar development involves a series of comparisons between the proposed biosimilar and reference performed in a step-wise fashion to eliminate any concerns regarding the similarity of the medicines. Randomized clinical trials (RCTs) are then performed to confirm that the reference product and its biosimilar provide the same clinical efficacy and safety. Patients with breast cancer (BC) are the most sensitive population in which to confirm similarity of G-CSF biosimilars, however there are some differences between clinical studies. The aim of this meta-analysis was to compare the safety profiles of approved or proposed G-CSF biosimilars (filgrastim or pegfilgrastim) with reference G-CSF in patients with BC. Methods: A Medline literature search up to March 2017 identified randomized clinical trials (RCTs) comparing biosimilar G-CSF to reference in BC patients. Safety analyses included calculation of risk ratios for bone pain events, myalgia events and serious adverse events. Random effect models were fitted to obtain the pooled estimates of the risk ratio for the outcomes and their corresponding 95% confidence intervals (CIs). Results: Eight eligible RCTs were included in this meta-analysis. Risk ratios for bone pain events (risk ratio 1.01 [95% CI -0.76, 1.34]; Table), myalgia events (risk ratio 0.94 [95% CI 0.63, 1.40]) and serious adverse events (risk ratio 1.01 [95% CI 0.76, 1.34]) showed no significant differences between reference and biosimilar G-CSF. Risk ratios for bone pain events BiosimilarsReference productsRisk RatioStudy and year of publicationReference G-CSF / Biosimilar G-CSFEventsTotalEventsTotalWeightIV, Random, 95% CIBlackwell 2015Filgrastim / Filgrastim331073810729.9%0.87 [0.59, 1.27]Blackwell 2016Pegfilgrastim / Pegfilgrastim101551715311.8%0.58 [0.27, 1.23]Harbeck 2016Pegfilgrastim / Pegfilgrastim715981577.3%0.86 [0.32, 2.33]Waller 2010Filgrastim / Filgrastim48183169521.1%1.56 [0.94, 2.59]Waller 2016Pegfilgrastim / Pegfilgrastim51127246729.7%1.12 [0.76, 1.65]Total (95% CI)731579100%1.01 [0.76, 1.34]Heterogeneity: Chi2 = 5.86, df = 4 (P = 0.21); I2 = 32% Test for overall effect: Z=0.07 (P=0.94) Conclusions: This meta-analysis showed no differences in the safety profile of biosimilar and reference G-CSF in breast cancer patients. Citation Format: Krendyukov A, Botteri E, Curigliano G. Safety of granulocyte colony-stimulating factors and their biosimilars: A meta-analysis of randomized clinical trials in breast cancer patients receiving cytotoxic chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-05.

The Efficacy and Safety of Granulocyte Colony-Stimulating Factor for Patients with Stroke

Granulocyte colony-stimulating factor (G-CSF) has been shown to reduce lesion volume and improve functional outcome in experimental stroke models. However, whether G-CSF plays a role currently in patients with stroke remains uncertain. Our study aimed at examining the efficacy and safety of G-CSF in patients with acute ischemic stroke. A comprehensive search was conducted in 5 online databases up to April 2014, and 10 studies with 711 patients met the criteria. The results showed that G-CSF was beneficial in improving the National Institutes of Health Stroke Scale (standardized mean difference [SMD], .43; 95% confidence interval [CI], .03-.82; P = .04) and modified Rankin Scale (mRS) scores (SMD, .72; 95% CI, .51-.93; P = .01), and elevating CD34(+) count (P < .001). No treatment effects were found in Barthel Index scores (SMD, -.13; 95% CI, -.61 to .35; P = .59), serious adverse events (relative ratio [RR], 1.12; 95% CI, .91-1.38; P = .28), or the death of serious adverse events (RR, 1.25; 95% CI, .82-1.91; P = .30) between groups at day 90. Adverse effect on vascular complications was not detected to be increased although G-CSF produced a marked elevation in the total leukocyte count (SMD, 3.52; 95% CI, 2.54-4.49; P < .001). In conclusion, G-CSF is effective at mobilizing bone marrow-derived CD34(+) stem cells to the peripheral blood. It also seems to improve the National Institutes of Health Stroke Scale and mRS scores. The administration of G-CSF appears to be safe and well tolerated. Further studies need to be done on a large sample to verify or fully characterize the results.

Safety of Granulocyte Colony-Stimulating Factor (G-CSF) Administration for Postrehabilitated Motor Complete Spinal Cord Injury Patients: An Open-Label, Phase I Study

Granulocyte colony-stimulating factor (G-CSF) is a major growth factor in the activation and differentiation of granulocytes. This cytokine has been widely and safely employed in different conditions over many years. In this translational study, G-CSF is administered to 19 patients with chronic motor complete spinal cord injury, and outcomes are reported. All 19 patients received subcutaneous G-CSF (5 µg/kg per day) for 5 days and were followed for at least 6 months. The American Spinal Injury Association (ASIA) scale was used for motor and sensory assessment, and the International Association of Neurorestoratology-Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS) and the Spinal Cord Independence Measure (SCIM) III were used to assess improvements in the ability to perform basic daily tasks. At the 6-month follow-up, upper extremity motor scores improved by 10, which was statistically significant (p = 0.007), whereas there were no significant changes in lower extremity motor scores. Also, the median of light touch sensory scores improved by 5 (p = 0.001). Pinprick sensory scores significantly improved (p = 0.002). The median increment in SCIM III total score was 7 (p = 0.001). The improvements in bladder and bowel management as well as moderate distance mobility subscales were also significant (p < 0.05). Total IANR-SCIFRS scores changed from 17 to 32, which was statistically significant (p = 0.001); again the bladder and bowel management subscale improvements were statistically significant (p < 0.05). Mild side effects of the G-CSF treatment such as bone pain, rash, fever, neuropathic pain, and spasticity were noted in a few patients; all of them resolved after 1 week. Our results indicate that G-CSF administration is a safe process and is associated with neurological as well as functional improvement. This manuscript is published as part of the International Association of Neurorestoratology (IANR) supplement issue of Cell Transplantation.

Intravenous administration of granulocyte colony-stimulating factor for treating neuropathic pain associated with compression myelopathy: a phase I and IIa clinical trial

To confirm the feasibility and safety of granulocyte colony-stimulating factor (G-CSF) for treating spinal neuropathic pain associated with compression myelopathy, we have initiated an open-label single-center prospective clinical trial. Between January 2009 and February 2011, 17 patients were accrued and were divided into two groups. One group included 7 patients who complained of pain associated with worsening symptoms of myelopathy (progressing myelopathy-related pain group). The other group included 10 patients who complained of pain that persisted after surgery for compression myelopathy (post-operative persistent pain group). All patients underwent intravenous administration of G-CSF (10 μg/kg/day) for 5 consecutive days. Pain severity was evaluated using a visual analog scale (VAS) before and after G-CSF administration. In 14 of the 17 patients, pain was relieved within several days after G-CSF administration. Pain disappeared completely in 3 patients. In the progressing myelopathy-related pain group, the mean VAS score was 71.4/100 before G-CSF administration, and decreased to 35.9/100 at 1 week after G-CSF administration (p < 0.05). In the post-operative persistent pain group, the mean VAS score was 72.0/100 before G-CSF administration, and decreased to 51.7/100 at 1 week after G-CSF administration (p < 0.05). No severe adverse events occurred during or after G-CSF administration. The present results provide us with the possibility that G-CSF has a pain-relieving effect for neuropathic pain in patients with compression myelopathy.

Safeguarding the long-term health of hematopoietic stem cell donors: a continuous and evolving process to maintain donor safety and trust

Safeguarding the long-term health of hematopoietic stem cell donors: a continuous and evolving process to maintain donor safety and trust

Use of granulocyte colony-stimulating factor in patients with severe sepsis or septic shock

The efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in critically ill patients with severe sepsis or septic shock were evaluated. The medical literature was reviewed to identify published trials, case reports, and case series on the use of G-CSF in critically ill patients for treatment of severe sepsis or septic shock. G-CSF has been evaluated as an adjunct to standard care for critically ill patients. Initial studies involving critically ill patients with severe sepsis or septic shock found mortality benefits with G-CSF therapy; however, these findings are limited by factors such as small sample sizes, selection bias, and lack of an appropriate control group. Prospective, randomized, multicenter, double-blind studies failed to confirm the benefits in mortality for patients receiving G-CSF for the treatment of severe sepsis and septic shock. Due to the limitations in the design of the studies that report a mortality benefit and prospective, randomized, multicenter, double-blind studies that report the lack of a mortality benefit, a recommendation to add G-CSF as an adjunctive therapy in critically ill patients with severe sepsis and septic shock cannot be made at this time. The available data, especially those from large, prospective, randomized, double-blind studies, do not support the use of G-CSF as an adjunct therapy to standard care for critically ill patients with severe sepsis or septic shock. Data from prospective, large, randomized, controlled, well-designed studies are needed to define the optimal G-CSF dosing regimen, the safety of this therapy, and the effects of G-CSF on patient morbidity and survival.

Granulocyte colony-stimulating factor for recalcitrant postherpetic neuralgia: a prospective, open, pilot study in three patients

Summary Recent experimental studies have shown that granulocyte colony-stimulating factor (G-CSF) has neuroprotective and regenerative properties in neuronal cells, suggesting its use as a potential treatment for recalcitrant postherpetic neuralgia (PHN). We evaluated the efficacy and safety of G-CSF in patients with recalcitrant PHN. Three patients with recalcitrant PHN were treated with subcutaneous injection of recombinant human G-CSF 10 μg/kg once daily for 5 days. Assessments were performed at baseline and at weeks 1, 4, 8, 12 and 48 using the Brief Pain Inventory (BPI) and the Clinician Global Impression (CGI) score. All patients found improvement in BPI and CGI scores throughout the study. We suggest that G-CSF may help alleviate neuropathic pain and improve the overall quality of life in patients with PHN.

Effects and safety of granulocyte colony-stimulating factor in healthy volunteers.

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) is now widely used in normal donors for collection of peripheral blood progenitor cells for allogeneic transplantation and granulocytes for transfusion. Currently available data on biologic and molecular effects, and safety of rhG-CSF in normal healthy volunteers are reviewed. In addition to its known activating role on neutrophil kinetics and functional status, rhG-CSF administration can affect monocytes, lymphocytes and the hemostatic system. Granulocyte colony-stimulating factor receptors were identified in a variety of nonmyeloid tissues, although their role and functional activity have not always been well defined. Moreover, rhG-CSF is capable of modulating complex cytokine networks and can impact the inflammatory response. In addition to its known mobilizing role for peripheral blood progenitor cells, rhG-CSF can mobilize dendritic and endothelial progenitor cells as well. On a clinical level, serious rhG-CSF-related adverse events are well described (e.g. splenic rupture) but remain rare. rhG-CSF effects in healthy volunteers, although normally transient and self-limiting, are now believed to be more complex and heterogeneous than previously thought. Although rhG-CSF administration to healthy volunteers continues to have a favorable risk-benefit profile, these new findings have implications for safeguarding the safety of normal individuals.

Current Status of Growth Factors in the Treatment of Acute Myeloid and Lymphoblastic Leukemia

The safety of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in patients with acute leukemia has been well established in numerous clinical trials. The primary aim of these studies was to determine whether CSFs, when used as adjuncts to intensive chemotherapy, reduced the duration of neutropenia, prevented febrile neutropenia, infections, and hospitalization rates, and improved response and overall outcome in patients with acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). Despite considerable efforts in divers clinical settings, the potential advantages of hematopoietic growth factors in the management of these leukemias remain inconclusive. In general, individual published trials have shown declines in the incidence and/or duration of neutropenia but have not consistently demonstrated a reduction in the overall frequency of infectious complications or the duration of hospitalization. Most protocols also have failed to show a benefit in terms of disease-free or overall survival. Nevertheless, improvements in "soft" clinical end points, such as incidence of severe infections, may be clinically important and contribute, even if only incrementally, to the patient's quality of life. Selection of those patients likely to benefit from growth factors in a specific clinical setting is a worthwhile endeavour.

Granulocyte-colony stimulating factor administration to healthy individuals and persons with chronic neutropenia or cancer: an overview of safety considerations from the Research on Adverse Drug Events and Reports project

Granulocyte-colony stimulating factor (G-CSF) is widely administered to donors who provide peripheral blood stem cells (PBSC) for individuals who undergo hematopoietic stem cell transplants. Questions have been raised about the safety of G-CSF in this setting. Herein, the Research on Adverse Drug Events and Reports (RADAR) project investigators reviewed the literature on G-CSF-associated adverse events in healthy individuals or persons with chronic neutropenia or cancer. Toxicities identified included bone pain and rare instances of splenic rupture, allergic reactions, flares of underlying autoimmune disorders, lung injury and vascular events. Among healthy individuals, four patients developed splenic rupture shortly after G-CSF administration and three patients developed acute myeloid leukemia 1 to 5 years after G-CSF administration. Registry studies identified no increased risks of malignancy among healthy individuals who received G-CSF before PBSC harvesting. However, more than 2000 donors would have to be followed for 10 years to detect a 10-fold increase in leukemia risk. Our review identifies bone pain as the most common toxicity of G-CSF administration. There are questions about a causal relationship between G-CSF administration and acute leukemia, but more long-term safety data from database registries are needed to adequately evaluate such a relationship.

Feasibility and safety of granulocyte colony-stimulating factor treatment in patients with acute myocardial infarction

Background This study examined feasibility and safety of granulocyte colony-stimulating factor (G-CSF) treatment for patients with acute myocardial infarction (AMI). Methods Forty patients with AMI related with the left anterior descending coronary artery, who underwent successful percutaneous coronary intervention (PCI), were randomized into G-CSF group ( n = 18) or Control group ( n = 22). G-CSF treatment was started within 24 h after PCI. 99mTc-tetrofosmin single-photon emission computed tomography (SPECT) was performed at 4 days and 6 months after AMI. SPECT data was analyzed for LV end-diastolic volume (LVEDV), LV end-systolic volume (LVESV), LV ejection fraction (LVEF) and myocardial perfusion. Results LVEF at 6 months was significantly better than that at 4 days in G-CSF group ( p = 0.013), but not changed in Control group ( p = 0.245). Although no significant difference was observed for LVEDV between the two groups, LVESV tended to be decreased only in G-CSF group. In G-CSF group, defect score (DS) was significantly decreased from 4 days to 6 months after AMI. Restenosis rate at 6 months after AMI was not significantly different between the two groups. Conclusions G-CSF treatment for patients with AMI was effective and did not have any clinical and angiographic adverse effects.