Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Filgrastim”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,135 records · Page 63Linked to original sources
PubMed1994

[Effect of granulocyte colony stimulating factor (G-CSF) on peripheral blood leukocytes and lymphocytes in patients with chemotherapy-induced leukopenia].

In patients with extensive chemotherapy, G-CSF abrogated leukopenia following administration of cytotoxic agents. Six women with ovarian cancer and chemotherapy-induced leukopenia received 300 micrograms Filgrastrim (r-metHuG-CSF, Neupogen 30; AMGEN, Germany) daily for 10 days. Leukocytes and lymphocyte subsets of peripheral blood were determined before, throughout and after subcutaneous injections of G-CSF by flow cytometry using monoclonal antibodies to CD3, CD4, CD8, CD14, CD16/56, CD19 and CD45. It could be observed that not only neutrophils (23 fold) but also lymphocytes (6 fold) and monocytes (10 fold) showed a dramatic increase in cell counts throughout and after G-CSF administration. This is in contrast to previous reports, where only effects on neutrophils were described. In spite of the increase in lymphocytes the relative percentage of CD3+, CD19+, CD3-CD16/CD56+, CD3+, CD8+ and CD3+ CD4+ lymphocyte subsets did not change throughout and after therapy, except for an increased expression of HLA-DR on CD3+ lymphocytes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

[Long-term treatment with recombinant human granulocyte colony stimulating factor in patients with severe congenital neutropenia].

Severe congenital neutropenia is a disorder of myelopoiesis characterized by severe neutropenia secondary to either a maturational arrest of myelopoiesis at the level of promyelocytes (Kostmann-Syndrome; SCN) or regular cyclic fluctuations in the number of blood neutrophils with a median ANC below 500/microliter (cyclic neutropenia). We have treated 32 patients with SCN and 4 patients with cyclic neutropenia. Thirty of 32 patients with SCN and all 4 patients with SCN responded to r-met HuG-CSF treatment with an increase of the median ANC to above 1000/microliter. The doses needed to achieve and maintain the response varied between 0.8 and 120 micrograms/kg/d. Long-term treatment did not exhaust the myelopoiesis: The mean ANC remained stable up to 5 years of treatment. The increase in ANC was associated with dramatic clinical responses: significant reduction of severe bacterial infections, reduction of intravenous antibiotic treatment episodes, and reduction of hospitalizations. No severe bacterial infections occurred in any of the r-met HuG-CSF responders during long-term treatment. Severe adverse event, most likely associated with the underlying disease, included the development of MDS/Leukemia in two patients, and osteopenia/osteoporosis in 12 patients. These results demonstrate the beneficial effects of r-met HuG-CSF treatment in severe congenital neutropenia patients.

Adolescent↗
PubMed1997

Granulocyte colony-stimulating factor in severe chemotherapy-induced afebrile neutropenia.

BACKGROUND: Randomized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit. Nevertheless, the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread. METHODS: We performed a randomized, double-blind, placebo-controlled trial of granulocyte colony-stimulating factor (G-CSF) in afebrile outpatients with severe chemotherapy-induced neutropenia. We measured the number of days of neutropenia, rate of hospitalization, number of days in the hospital, number of days the patient received parenteral antibiotics, and number of culture-positive infections. RESULTS: We randomly assigned 138 patients to receive G-CSF (n=71) or placebo (n=67). The median time to an absolute neutrophil count of at least 500 per cubic millimeter was significantly shorter for patients who received G-CSF (two days, vs. four days for the patients given placebo). However, there was no effect on the rate of hospitalization, number of days in the hospital, duration of treatment with parenteral antibiotics, or number of culture-positive infections. CONCLUSIONS: Routine therapeutic application of G-CSF in afebrile patients with severe neutropenia can reduce the duration of neutropenia, but this does not appear to provide practical clinical benefit.

Adult↗
PubMed1997

Human granulocyte colony-stimulating factor after induction chemotherapy in children with acute lymphoblastic leukemia.

BACKGROUND: Recombinant human granulocyte colony-stimulating factor PO1 CA-20180ilgrastim) hastens the recovery from neutropenia after P30 CA-21765emotherapy, but its role in the management of childhood leukemia is unclear. METHODS: We randomly assigned 164 patients with acute lymphoblastic leukemia (age range, 2 months to 17 years) to receive placebo or G-CSF (10 microg per kilogram of body weight per day subcutaneously), beginning one day after the completion of remission-induction therapy and continuing until the neutrophil count was greater than or equal to 1000 per cubic millimeter for two days. The clinical and laboratory effects of this therapy were documented for 21 days. The area under the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both groups. RESULTS: Responses to the growth factor could be assessed in 148 patients (73 in the G-CSF group and 75 in the placebo group). G-CSF treatment did not significantly lower the rate of hospitalization for febrile neutropenia (58 percent in the G-CSF group vs. 68 percent in the placebo group; relative risk, 0.85; 95 percent confidence interval, 0.59 to 1.16), increase the likelihood of event-free survival at three years (83 percent in both groups), or decrease the number of severe infections (five in the G-CSF group vs. six in the placebo group). Patients treated with G-CSF had shorter median hospital stays (6 days vs. 10 days, P=0.011) and fewer documented infections (12 vs. 27, P=0.009). The median total costs of supportive care were similar in the G-CSF and placebo groups ($8,768 and $8,616, respectively). Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections, higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization (P=0.049). CONCLUSIONS: G-CSF treatment had some clinical benefit in children who received induction chemotherapy for acute lymphoblastic leukemia, but it did not reduce the rate of hospitalization for febrile neutropenia, prolong survival, or reduce the cost of supportive care.

Adolescent↗
PubMed2002

Granulocyte colony-stimulating factor primes NADPH oxidase in neutrophils through translocation of cytochrome b(558) by gelatinase-granule release.

Granulocyte colony-stimulating factor (GCSF) primes reduced neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in response to formyl peptide but does not increase oxidase activity when used alone. Both oxidase activity and degranulation require phospholipase D (PLD) activation, and exogenous C(2)-ceramide inhibits both functions through inhibition of PLD activity. We extended these observations to investigate neutrophil responses to GCSF. GCSF at a dosage of 30 to 100 ng/mL, a concentration range that primes superoxide release, stimulated a 60% to 100% increase in gelatinase release from tertiary granules but did not stimulate lactoferrin release from secondary granules. A 75% to 100% dose-dependent increase in PLD activity in GCSF-treated neutrophils was also observed. Gelatinase release and PLD activity were inhibited by 10 micromol/L C(2)-ceramide. The increase in gelatinase release in response to priming concentrations of GCSF suggests that tertiary granules contribute a component of the NADPH oxidase to the plasma membrane. Neutrophils treated with 50 ng/mL GCSF were found to contain 20% more cytochrome b(558) in the plasma membrane fraction than unstimulated cells, consistent with degranulation of only tertiary granules. Correspondingly, in the presence of 10 micromol/L C(2)-ceramide, cytochrome b(558) content in the plasma membrane did not increase after neutrophil activation. In contrast, GCSF did not lead to p47phox translocation to the plasma membrane or phosphorylation. Because phosphorylation and translocation of p47phox are required for oxidase activity, these findings account for the inability of GCSF alone to generate the respiratory burst. We conclude that translocation of cytochrome b(558) was responsible for GCSF priming of NADPH oxidase in neutrophils.

Cell Membrane↗
PubMed1998

Cancer treatment in Sweden--costs of drugs, inpatient and outpatient care from 1985 to 1996 and cost effectiveness of new drugs.

This study was carried out to investigate the direct costs for treatment of patients with cancer from 1985 to 1996 in Sweden, and to examine health economic effects of changes in treatment pattern. Material for the study was collected from official statistics and from published health economic evaluations of cancer treatment. Costs for inpatient care decreased during the period, while costs for outpatient care and drugs increased. In total, the direct health care costs for cancer treatment decreased from 1985 to 1996. New drugs registered on the market are often more expensive than the drugs they replace. From a health economic perspective it is not clear, however, that higher drug costs necessarily increase total costs. Further health economic research is needed because many treatment alternatives have not yet been evaluated, and furthermore, because a treatment option can be cost effective in one specific indication but not in another.

Ambulatory Care↗
PubMed2005

Ultrafiltered pig leukocyte extract (UPLE, IMUNOR) potentiates hematopoiesis-stimulating effects of G-CSF in vitro and improves the outcome of treatment of hematopoietic radiation damage in mice with G-CSF.

Ultrafiltered pig leukocyte extract (UPLE, Imunor), a heterogeneous mixture of low molecular weight (<10 kD) substances released from disintegrated pig leukocytes was tested from the point of view of its hematopoiesis-modulating activities using experiments in vitro and in vivo. Attention was focused especially on evaluation of the contingent ability of UPLE to potentiate the hematopoiesis-stimulating effects of recobinant human granulocyte colony-stimulating factor (G-CSF). Experiments in vitro revealed the capability of sera from mice administered UPLE perorally (p.o.) to stimulate proliferation of progenitor cells for granulocytes and macrophages (GM-CFC) in cultures of normal bone marrow cells. In addition, UPLE, as well as sera from mice given UPLE, added to the cultures in combination with G-CSF enhanced the numbers of GM-CFC significantly over those induced by sera after administration of either of the preparations alone. In in vivo experiments, UPLE was found to increase the counts of GM-CFC per femur and femoral bone marrow cellularity in sublethally irradiated mice when administered p.o. after irradiation in combination with G-CSF in comparison with the effects of G-CSF alone. These results indicate the possibility of using UPLE, a commercially available preparation, for treatment of hematopoietic suppression of various etiology.

Animals↗
PubMed2003

Decreased transfusion requirements in patients given stem cell allografts using a non-myeloablative conditioning regimen: a single institution experience.

We report our experience of allogeneic peripheral blood stem cell transplantation using non-myeloablative conditioning regimens delivered and supported on an outpatient basis. A group of 44 patients underwent 47 allograft procedures using peripheral blood stem cells. Approximately one third of the individuals did not require red blood cells transfusions: the median of transfused red blood cells units was 1 (range 0-10). In addition one out of three did not require platelet transfusions either, the median of platelet transfusions being 1 (range 0-6). In fourteen allografts (30%) neither red blood cells nor platelet transfusions were used. An inverse correlation was found between the number of CD34 cells infused and the PRBC and PLT transfusion requirements, those patients receiving high numbers of CD34 cells needing fewer transfusions of both PRBC and platelets. The possibility of conducting allografts without transfusion of blood products in some patients may result in a decrease in both cost and the risks stemming from exposure to human blood derivatives.

Adolescent↗
PubMed2003

Fixed-dose pegfilgrastim is safe and allows neutrophil recovery in patients with non-Hodgkin's lymphoma.

Twenty-nine patients with non-Hodgkin's lymphoma received a single subcutaneous injection of 6 mg pegfilgrastim approximately 24 h after the start of CHOP chemotherapy. The safety of pegfilgrastim in this patient population was determined by reports of adverse events. The pharmacokinetics of pegfilgrastim were characterized and the duration of grade 4 neutropenia, time to absolute neutrophil count (ANC) recovery to > or = 2.0 x 10(9)/l, neutrophil nadir, and incidence of febrile neutropenia were determined in the first 21-day chemotherapy cycle. The incidence of grade 4 neutropenia in cycle 1 was 43% with a mean (SD) duration of grade 4 neutropenia value of 1.0 (1.4) day. No apparent relationship between the duration of grade 4 neutropenia and body weight was observed. The median [quartiles] time to ANC recovery was 10 [9, 11] days. The incidence of febrile neutropenia was 11%. No unexpected adverse events were reported and no patient developed antibodies to pegfilgrastim. Serum concentration of pegfilgrastim reached a maximum (median [quartiles]) of 128 [58, 159] ng/ml at approximately 24 h after administration, and was followed by a second smaller peak (median [quartiles]) of 10.6 [3.0, 20.5] ng/ml at the time of the neutrophil nadir. After the second peak, concentration of pegfilgrastim declined linearly with a median terminal half-life of approximately 42 h.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Guillain-Barré syndrome complicating mobilization therapy in a case of B-cell chronic lymphocytic leukemia.

We report a case of Guillain-Barré Syndrome (GBS) which appeared after mobilization therapy in a patient with B-cell chronic lymphocytic leukemia (B-CLL). After obtaining a partial remission with four cycles of fludarabine at standard dose, the patient underwent to high-dose Cytoxan in order to mobilize CD34+ hematopoietic progenitor cells. During neutropenia the patient experienced fever of unknown origin (FUO) and subsequently developed GBS with normalization of his neurologic condition after 2 months. It is possible that a viral-induced activation of an antigen-specific T and B-cell clone caused a local inflammation and toxicity of Schwann cells with demyelination and axonal damage with a self-limited course.

Adult↗
PubMed2006

Pegfilgrastim administered in a single fixed dose is effective in inducing neutrophil count recovery after paclitaxel and topotecan chemotherapy in patients with relapsed aggressive non-Hodgkin's lymphoma.

Pegfilgrastim is a pegylated form of a granulocyte colony-stimulating factor with a long half-life allowing for a single administration per chemotherapy cycle. The efficacy of a single dose of pegfilgrastim in supporting severely myelosuppressive regimens in previously treated cancer patients is unknown. Patients included in the present study had recurrent or refractory aggressive non-Hodgkin's lymphoma (NHL), had received two to three prior treatment regimens, and had good performance status and marrow reserve. Patients received intravenous paclitaxel 200 mg/m(2) on day 1 and topotecan 1 mg/m(2) daily for 5 days, repeated every 21 days for at least two cycles. On day 6, patients were given a single fixed dose of pegfilgrastim (6 mg) subcutaneously. Twenty patients were evaluable for analysis. After the first course of therapy, grade 4 neutropenia developed in all 20 patients. The median time to the neutrophil nadir was 9 days. The mean +/- SD duration of grade 4 neutropenia was 3.8 +/- 1.7 days. Nineteen (95%) patients received cycle 2 on time, on day 22. Five patients developed neutropenic fever (25%), which was associated with infection in one patient. In these previously treated patients with NHL, a single dose of pegfilgrastim was effective in promoting neutrophil count recovery after paclitaxel and topotecan, and allowed patients to receive the next planned dose on time.

Adult↗
PubMed2006

Safety and efficacy of pegfilgrastim compared to granulocyte colony stimulating factor (G-CSF) supporting a dose-intensive, rapidly cycling anti-metabolite containing chemotherapy regimen (Hyper-CVAD) for lymphoid malignancy.

Pegfilgrastim (Neulasta) has proven efficacy as supportive therapy in a variety of 21-day chemotherapy regimens, but has not been studied in dose intensive, rapidly cycling regimens utilising cell-cycle active drugs (e.g. anti-metabolites) such as hyper-CVAD. This study examined whether pegfilgrastim was safe and lead to similar kinetics of neutrophil recovery as daily granulocyte colony stimulating factor (G-CSF). Using retrospective analysis, patients receiving pegfilgrastim (6 mg) were matched with controls (G-CSF 5 microg kg-1 per day) for a cycle of chemotherapy, prior chemotherapy, dose of cytarabine received, age (<60 or >60 years), diagnosis and bone marrow involvement. The primary endpoint was duration of grade IV neutropenia (absolute neutrophil count, ANC < 500 microl-1). Secondary endpoints included time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy. This study identified 124 pegfilgrastim supported cycles in 43 patients and successfully matched them to 124 G-CSF supported cycles from 38 patients treated between January 1999 and July 2005. There were no significant differences between pegfilgrastim and G-CSF groups in baseline or treatment-related variables. The median duration of grade IV neutropenia was 4 days in both groups (P = 0.55). Time to neutrophil recovery, incidence of febrile neutropenia, positive blood cultures and delay in subsequent chemotherapy were similar in both groups. Once per cycle dosing of pegfilgrastim appears safe and as effective as daily G-CSF for supporting the hyper-CVAD chemotherapy regimen.

Adult↗
PubMed2006

Pegfilgrastim to support CHOP-14 in elderly patients with non-Hodgkin's lymphoma.

This study investigated whether pegfilgrastim support would enable on-schedule delivery of dose-dense cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP-14) to elderly patients with non-Hodgkin's lymphoma (NHL). Thirty patients 60 years of age and older with aggressive NHL were evaluated after receiving up to six cycles of CHOP-14 supported with pegfilgrastim. The median age was 68 years (range 61 - 74). Forty-seven per cent of patients received full dose chemotherapy on schedule for all cycles (range 65 - 93). Chemotherapy was delayed in 10 patients and dose reduced in 15 patients. Hematological toxicity was the most common reason for delays and dose reduction. Six of nine patients (67%) achieved a peripheral blood CD34+ count of at least 20 cellsx106 L-1 on day 12 of cycle one. The delivery on schedule of dose-dense CHOP-14 to elderly patients with previously untreated aggressive NHL is safe and efficacious with once per cycle pegfilgrastim support.

Aged↗
PubMed2000

Treatment of orogastrointestinal candidosis in SCID mice with fluconazole alone or in combination with recombinant granulocyte colony-stimulating factor or interferon-gamma.

Mucosal candidosis is common in acquired immune deficiency syndrome (AIDS) patients, where there is extensive mucosal involvement, but rarely dissemination. To mimic this disease, SCID mice were inoculated orally with Candida albicans, which could be recovered from standardized tissue samples of the esophagus, stomach, small intestine and caecum of all mice. Treatment with fluconazole at 5 or 10 mg kg(-1) per day were equivalent to each other and efficacious in reducing the fungal burden from all four tissues compared with no treatment or lower doses of fluconazole (P < 0.01-0.001). Fluconazole at 5 or 10 mg kg(-1) reduced fungal burden in the stomach by about 200 or 580-fold, respectively, and by approximately 25-fold in the other tissues, with 80 or 100% of mice cleared of esophageal infection, and 40 or 80% cleared of infection in the small intestine, respectively; the same doses cleared < or =20% of stomach infection and none of caecal infection. Treatment with recombinant human granulocyte colony-stimulating factor (G-CSF) up to 500 microg kg(-1) per day or 10(5) U of murine interferon-gamma (IFN-gamma) alone was ineffective, nor were combinations with a suboptimal dose fluconazole synergistic. Overall, fluconazole had dose-responsive efficacy, whereas neither G-CSF nor IFN-gamma alone or in combination with fluconazole improved efficacy. These studies demonstrate the utility of this model for examining antifungal efficacy in a situation that mimics clinical disease in AIDS patients.

Animals↗
PubMed2000

Human accessory cells have a humoral bystander effect on CAFC growing on murine feeder.

Human early hematopoietic progenitors from bone marrow (BM) and leukapheresis products (LP) are highly proliferative in presence of accessory cells in standard culture on the murine FBMD-1 cell feeder with weekly addition of human interleukin-3 (HuIL-3) and granulocyte-colony stimulating factor (HuG-CSF). If however purified CD34+ cells are cultured under otherwise identical conditions, cobblestone areas (CAFC) formed by the same number of target cells are diminished by more than 1 log, as we showed previously. This suggests that mature cells are involved in growth of early progenitors. To determine whether this bystander effect is mediated by soluble growth factors, or by direct cell-to-cell contact with early progenitors, we stimulated mature plastic adherent cells separately and tested the resulting conditioned supernatant (ACS) on CAFC and colony-forming unit-granulocyte-macrophage (CFU-GM) production. In ACS-complemented standard cultures of purified CD34+ cells, the yield of CAFC was up to 1 log higher if compared to parallel cultures without ACS. Likewise, the CFU-GM production was enhanced in presence of ACS, especially in the adherent fraction of the culture. When CD34+ cell cultures were performed with ACS but without added interleukin-3 (IL-3) and granulocyte colony-stimulating factor (G-CSF), CAFC production was in the same range as if these growth factors were added alone. Addition of anti-G-CSF antibody (Ab) to ACS decreased CAFC recruitment significantly, whereas anti-IL-3 Ab had no significant effect. These findings suggest that ACS complemented with IL-3 and G-CSF replaces the accessory cells largely; this is not only due to presence of G-CSF, because ACS in combination with recombinant growth factors mounts CAFC yield higher than saturating amounts of growth factors alone do. There must be further synergizing soluble factors in the supernatant.

Animals↗
PubMed2002

Proteolytic enzyme levels are increased during granulocyte colony-stimulating factor-induced hematopoietic stem cell mobilization in human donors but do not predict the number of mobilized stem cells.

Previous studies from our laboratory indicate that functional, mature neutrophils are essential for interleukin-8 (IL-8)-induced stem cell mobilization. To study a possible role of neutrophils in granulocyte colony-stimulating factor (G-CSF) induced hematopoietic mobilization, we assessed the number of circulating CD34+ cells in healthy allogeneic stem cell donors on days 3, 4, and 5 of mobilization for comparison with the number of peripheral blood neutrophils and the plasma levels of IL-8, Flt3 ligand (FL), matrix metalloproteinase-9 (MMP-9), and human neutrophil elastase (HNE). Thirty-seven of 45 donors required 1 day of apheresis to obtain 5 x 10(6) CD34+/kg recipient body weight (high responders), the remaining 8 donors required 1 extra day of apheresis on day 6 (low responders). On day 5, CD34+ numbers in the blood were significantly highe in high responders (116 x 10(3) +/- 10.4/ml) than in low responders (54.1 x 10(3) +/- 10.3, p < 0.001). In all donors, MMP-9 and HNE levels were increased compared to nonmobilized individuals, but in high responders, plasma MMP-9 levels on days 3-5 of mobilization were substantially higher than in low responders (p < or = 0.02 for MMP-9 and p = 0.89, p = 0.05 and p = 0.52 for HNE on days 3, 4, and 5, respectively). These results are in accordance with the hypothesis that neutrophils play a role in G-CSF-induced mobilization through the release of proteases such as MMP-9 and elastase. No change in plasma levels of IL-8 or Flt3 ligand was observed, suggesting that these cytokines do not play a role in stem cell mobilization. However, because stem cell numbers could not be predicted by proteolytic enzyme levels and/or neutrophil numbers, other undefined factors may be more important.

Antigens, CD34↗