Relationship Between Absolute Neutrophil Count Profiles and Pharmacokinetics of DA-3031, a Pegylated Granulocyte Colony-Stimulating Factor (Pegylated-G-CSF): A Dose Block-Randomized, Double-Blind, Dose-Escalation Study in Healthy Subjects

2013 ◽  
Vol 33 (11) ◽  
pp. 817-824 ◽  
Author(s):  
Li Young Ahn ◽  
Kwang-Hee Shin ◽  
Kyoung Soo Lim ◽  
Tae-Eun Kim ◽  
Hyewon Jeon ◽  
...  
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Dose Escalation ◽  
Healthy Subjects ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Stimulating Factor

scholarly journals A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2496-2502 ◽  
Author(s):  
DC Dale ◽  
MA Bonilla ◽  
MW Davis ◽  
AM Nakanishi ◽  
WP Hammond ◽  
...  
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Bacterial Infections ◽  
Phase Iii ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Phase Iii Trial ◽  
Duration Of Infection ◽  
Stimulating Factor ◽  
Chronic Neutropenia

Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony- stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of = or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.

scholarly journals A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia

Blood ◽  
1993 ◽  
Vol 81 (10) ◽  
pp. 2496-2502 ◽  
Author(s):  
DC Dale ◽  
MA Bonilla ◽  
MW Davis ◽  
AM Nakanishi ◽  
WP Hammond ◽  
...  
Keyword(s):  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Bacterial Infections ◽  
Phase Iii ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Phase Iii Trial ◽  
Duration Of Infection ◽  
Stimulating Factor ◽  
Chronic Neutropenia

Abstract Patients with idiopathic, cyclic, and congenital neutropenia have recurrent severe bacterial infections. One hundred twenty-three patients with recurrent infections and severe chronic neutropenia (absolute neutrophil count < 0.5 x 10(9)/L) due to these diseases were enrolled in this multicenter phase III trial. They were randomized to either immediately beginning recombinant human granulocyte colony- stimulating factor (filgrastim) (3.45 to 11.50 micrograms/kg/d, subcutaneously) or entering a 4-month observation period followed by filgrastim administration. Blood neutrophil counts, bone marrow (BM) cell histology, and incidence and duration of infection-related events were monitored. Of the 123 patients enrolled, 120 received filgrastim. On therapy, 108 patients had a median absolute neutrophil count of = or = 1.5 x 10(9)/L. Examination of BM aspirates showed increased proportions of maturing neutrophils. Infection-related events were significantly decreased (P < .05) with approximately 50% reduction in the incidence and duration of infection-related events and almost 70% reduction in duration of antibiotic use. Asymptomatic splenic enlargement occurred frequently; adverse events frequently reported were bone pain, headache, and rash, which were generally mild and easily manageable. These data indicate that treatment of patients with severe chronic neutropenia with filgrastim results in a stimulation of BM production and maturation of neutrophils, an increase in circulating neutrophils, and a reduction in infection-related events.

162 Add-on Filgrastim During Clozapine Rechallenge Unsuccessful in Treating Benign Ethnic Neutropenia

CNS Spectrums ◽  
2018 ◽  
Vol 23 (1) ◽  
pp. 98-99 ◽  
Author(s):  
Molly Britton ◽  
Palanikumar Gunasekar ◽  
Vithyalakshmi Selvaraj
Keyword(s):  
Suicidal Behavior ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Middle Eastern ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Treatment Resistant ◽  
Clozapine Treatment ◽  
Stimulating Factor ◽  
Funding Acknowledgements

AbstractClozapine is an atypical antipsychotic approved by the Food and Drug Administration for treatment-resistant schizophrenia and also indicated for the reduction in risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder. The most serious side effect of clozapine treatment is agranulocytosis, which is defined as an absolute neutrophil count (ANC) < 0.50 × 109 per L. Benign ethnic neutropenia (BEN) is a condition found in members of African or Middle Eastern descent that is characterized by ANC < 1.50 × 109 per L in the absence of other causes. Filgrastim is a granulocyte colony-stimulating factor (G-CSF) that has shown efficacy in reducing the duration of agranulocytosis in some patients who develop clozapine-induced agranulocytosis. It is currently unknown whether filgrastim is beneficial in the treatment of neutropenia due to BEN. We here, for first the time report a case of a patient with BEN who developed agranulocytosis both during the first clozapine trial for schizophrenia and during the rechallenge, despite early stabilization with filgrastim treatment, which highlights the failure of filgrastim in treating BEN.Funding AcknowledgementsNo funding.

scholarly journals Human granulocyte-colony stimulating factor (G-CSF)/stem cell factor (SCF) fusion proteins: design, characterization and activity

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e9788
Author(s):  
Gitana Mickiene ◽  
Indrė Dalgėdienė ◽  
Gintautas Zvirblis ◽  
Zilvinas Dapkunas ◽  
Ieva Plikusiene ◽  
...  
Keyword(s):  
Stem Cell ◽  
Western Blot ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Fusion Proteins ◽  
Stem Cell Factor ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Rp Hplc ◽  
Stimulating Factor

Background Stem cell factor (SCF) and granulocyte-colony stimulating factor (G-CSF) are well-characterized vital hematopoietic growth factors that regulate hematopoiesis. G-CSF and SCF synergistically exhibit a stimulatory effect on hematopoietic progenitors. The combination of G-CSF and SCF has been used for mobilization of peripheral blood progenitor cells in cancer and non-cancerous conditions. To overcome challenges connected with the administration of two cytokines, we developed two fusion proteins composed of human SCF and human G-CSF interspaced by an alpha-helix-forming peptide linker. Methods The recombinant proteins SCF-Lα-GCSF and GCSF-Lα-SCF were purified in three steps using an ion-exchange and mixed-mode chromatography. The purity and quantity of the proteins after each stage of purification was assessed using RP-HPLC, SDS-PAGE, and the Bradford assays. Purified proteins were identified using high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) and the Western blot analyses. The molecular weight was determined by size exclusion HPLC (SE-HPLC). The activity of heterodimers was assessed using cell proliferation assays in vitro. The capacity of recombinant fusion proteins to stimulate the increase of the absolute neutrophil count in rats was determined in vivo. The binding kinetics of the proteins to immobilized G-CSF and SCF receptors was measured using total internal reflection ellipsometry and evaluated by a standard Langmuir kinetics model. Results The novel SCF-Lα-GCSF and GCSF-Lα-SCF proteins were synthesized in Escherichia coli. The purity of the heterodimers reached >90% as determined by RP-HPLC. The identity of the proteins was confirmed using the Western blot and HPLC/ESI-MS assays. An array of multimeric forms, non-covalently associated dimers or trimers were detected in the protein preparations by SE-HPLC. Each protein induced a dose-dependent proliferative response on the cell lines. At equimolar concentration, the heterodimers retain 70–140% of the SCF monomer activity (p ≤ 0.01) in promoting the M-07e cells proliferation. The G-CSF moiety in GCSF-Lα-SCF retained 15% (p ≤ 0.0001) and in SCF-Lα-GCSF retained 34% (p ≤ 0.01) of the monomeric G-CSF activity in stimulating the growth of G-NFS-60 cells. The obtained results were in good agreement with the binding data of each moiety in the fusion proteins to their respective receptors. The increase in the absolute neutrophil count in rats caused by the SCF-Lα-GCSF protein corresponded to the increase induced by a mixture of SCF and G-CSF.

scholarly journals Perbandingan Efektivitas Produk Filgrastim pada Pasien Keganasan Limfoma yang Menerima Kemoterapi di RSUP dr. Sardjito Yogyakarta

2019 ◽  
Vol 4 (1) ◽  
pp. 9
Author(s):  
Dhien Setiani
Keyword(s):  
Cohort Study ◽  
Absolute Neutrophil Count ◽  
Neutrophil Count ◽  
Recovery Time ◽  
Goodness Of Fit ◽  
Granulocyte Colony Stimulating Factor ◽  
Colony Stimulating Factor ◽  
Chi Square ◽  
Kaplan Meier ◽  
Stimulating Factor

Neutropenia adalah toksisitas yang sering terjadi pada pasien kanker limfoma akibat menerima kemoterapi mielotoksik. Granulocyte Colony Stimulating Factor (G-CSF) direkomendasikan secara klinik untuk neutropenia. Filgrastim adalah nama generik dari merk produk G-CSF yang beredar di Indonesia seperti Filgrastim merk A dan Filgrastim merk B yang diproduksi oleh pabrik yang berbeda. Perbedaan Filgrastim merk A dan Filgrastim merk B selain pabrik yang memproduksi adalah harga produk Filgrastim A lebih murah dibandingkan Filgrastim merk B. Perbandingan efektivitas Filgrastim merk A dengan Filgrastim merk B pada pasien di RSUP Dr.Sardjito Yogyakarta perlu diteliti untuk evaluasi terhadap efektivitas jenis obat yang telah dipakai secara klinik. Tujuan penelitian ini adalah membandingkan efektivitas Filgrastim merk A dan Filgrastim merk B pada penggunaan praktek klinik sehari-hari di RSUP Dr. Sardjito Yogyakarta. Rancangan penelitian ini menggunakan analitik retrospektif cohort study pada pasien yang menerima kemoterapi di Instalasi Kanker Tulip RSUP Dr. Sardjito Yogyakarta. Data diambil dari rekam medik periode Januari 2013 sampai Maret 2015. Perbandingan efektivitas filgrastim menggunakan parameter waktu untuk mencapai Absolute Neutrophil Count (ANC) recovery. Data karakteristik subjek penelitian dianalisis menggunakan Chi Square Goodness of Fit untuk data kategorik dan uji t independent untuk data numerik. Perbandingan efektivitas filgrastim merk A dan merk B dianalisis menggunakan analisis survival. Diperoleh sebanyak 80 subjek pasien keganasan limfoma dengan 192 episode kejadian neutropenia yang mendapatkan terapi filgrastim. Dari 80 subjek, hanya 43 subjek (53,5%) yang terdiri dari 72 episode kejadian neutropenia) yang memenuhi kriteria inklusi (33 kejadian memakai filgrastim merk A dan 39 kejadian filgrastim merk B). Hasil perbandingan efektivitas filgrastim berdasarkan kecepatan waktu meningkatkan ANC recovery menurut analisis survival bivariat Kaplan Meier,dengan data pengamatan laboratorium 24 jam post suntik terakhir, menunjukkan bahwa Filgrastim merk A memiliki median recovery time lebih Perbandingan Efektivitas Produk Filgrastim Pasien Keganasan Limfoma yang Menerima Kemoterapi cepat dibandingkan Filgrastim merk B ( 1,00 vs 2,00 hari ;p < 0,05). Kesimpulan penelitian ini adalah Filgrastim merk A lebih efektif dibandingkan Filgrastim merk B dalam hal kecepatan waktu untuk mencapai ANC recovery.

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