Differences in functional activity and antigen expression of granulocytes primed in vivo with filgrastim, lenograstim, or pegfilgrastim

Ribeiro, Daniel Melo; Veldwijk, Marlon R.; Benner, Axel; Laufs, Stephanie; Wenz, Frederik; Ho, Anthony D.; Früehauf, Stefan

doi:10.1111/j.1537-2995.2007.01241.x

Cited by 32 publications

(31 citation statements)

References 59 publications

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“…32 Moreover, there is experimental evidence that the quantity of sugars linked to proteins (glycosylation rate is 4% of its MW) is important in determining neutrophil activities. Neutrophils mobilized by lenograstim (glycosylated G-CSF) display a higher expression of the maturity markers 33 involved in recognition, adhesion, phagocytosis and interaction with Igs. The underlying mechanism for these greater effects remains elusive.…”

Section: Discussionmentioning

confidence: 99%

Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs

Ria

Gasparre

Mangialardi

et al. 2009

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 99%

Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs

Ria

Gasparre

Mangialardi

et al. 2009

Bone Marrow Transplant

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“…Both G-CSF and G-CSFR are glycoproteins (20); therefore, additional glycosylation in the hG-CSF ligand could potentially increase the receptor binding affinity because of glyco-glyco interactions (21). G-CSF also plays a critical role in chemotaxis and differentiation in hematopoietic stem cells (2). G-CSF induces the migration of hematopoietic stem cells to injured tissues where they participate in the immune response (22).…”

Section: Discussionmentioning

confidence: 99%

“…Survivin plays a role in the proliferation of leukemic cell lines and has an anti-apoptotic function (9). In addition, G-CSF also has a chemoattractant activity and induces the differentiation of HL60 and bone marrow stem cells into neutrophils (2). In general, glycosylation is critical for the biological activity of numerous molecules (10).…”

Section: Introductionmentioning

confidence: 99%

“…A number of cytokines, such as erythropoietin (EPO) and colony-stimulating factors (CSFs), are currently used for the treatment of diseases, such as cancer and blood deficiencies (1,2). Among them, human granulocyte CSF (hG-CSF) is a hematopoietic factor that plays an important role in stimulating the proliferation, differentiation, and functional activation of blood cells (3).…”

Section: Introductionmentioning

confidence: 99%

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Enhanced biological effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant, on HL60 cells

Chung¹,

Kim²,

Byun³

et al. 2011

BMB Reports

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Granulocyte colony-stimulating factor (G-CSF) is a cytokine secreted by stromal cells and plays a role in the differentiation of bone marrow stem cells and proliferation of neutrophils. Therefore, G-CSF is widely used to reduce the risk of serious infection in immunocompromised patients; however, its use in such patients is limited because of its non-persistent biological activity. We created an N-linked glycosylated form of this cytokine, hG-CSF (Phe140Asn), to assess its biological activity in the promyelocyte cell line HL60. Enhanced biological effects were identified by analyzing the JAK2/STAT3/survivin pathway in HL60 cells. In addition, mutant hG-CSF (Phe140Asn) was observed to have enhanced chemoattractant effects and improved differentiation efficiency in HL60 cells. These results suggest that the addition of N-linked glycosylation was successful in improving the biological activity of hG-CSF. Furthermore, the mutated product appears to be a feasible therapy for patients with neutropenia. [BMB reports 2011; 44(10): 686-691]

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“…Lo studio delle caratteristiche immunofenotipiche dei neutrofili stimolati con fattori di crescita ha evidenziato che lenograstim determina la formazione di neutrofili, maturi e quindi normofunzionanti. Al contrario, con filgrastim, probabilmente per un meccanismo di stimolazione midollare non fisiologica, i neutrofili risultano avere un immunofenotipo più immaturo che quindi li fa risultare ipofunzionanti a seguito di stimolazioni batteriche (Figura 3,4) [3,16,17]. Le differenze fra lenograstim e filgrastim trovano i primi riscontri anche in clinica.…”

Section: Efficaciaunclassified

Appropriate administration of Granulocyte-Colony Stimulating Factors

Rosti¹

2012

RHC

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Chemotherapy-induced febrile neutropenia is a potentially fatal complication of cancer treatment and is also the main reason of dose-reduction and/or delay of chemotherapy regimen. Prophylaxis with G-CSF is applicable to reduce the risk of chemotherapy-induced neutropenia. Two molecules of recombinant G-CSF are available for clinical use: lenograstim, identical to human native G-CSF, that is derived from mammalian cells and filgrastim, different to human native G-CSF, expressed in E. coli and commercialized in normal form and pegilated long-acting form. Neutrophil morphology and expected defense functions are modified by treatment with filgrastim, while they are not affected by lenograstim. These functionality differences observed in vitro are recently confirmed in a clinical trial that shows a lower incidence of febrile episodes with lenograstim compared to filgrastim in presence of G-CSF induced neutrophils. The long-term safety of lenograstim was supported by the results of a prospective, longer-term study involving almost 4,000 healthy donors. Another important question is the respect of timing of administration of G-CSF and chemotherapy. Absolutely in no case the plasma concentration of G-CSF is to be detected 48h before to 24h post chemotherapeutic drugs administration. In fact, this combination could result in an increased risk of mielotoxicity and a potential for an increase in sensitivity of rapidly dividing myeloid cells to cytotoxic-mutagenic chemotherapy potential. Lenograstim and filgrastim shows short half-life time, instead pegfilgrastim shows detectable concentrations for 16 days after a single administration. This is important to be considered, in particular in bi-weekly and tri-weekly adjuvant chemotherapy regimens. Anyway, the use of the lowest effective dose for the shortest adequate time of medications ensures the optimal balance among effectiveness, safety and costs of treatments, in a context that takes into account effectiveness and efficiency.Keywords Granulocyte-Colony Stimulating Factors; Lenograstim; Filgrastim; Pegfilgrastim; G-CSF; Timing; Appropriateness; Guidelines Appropriatezza d'uso dei fattori di crescita granulocitari nella profilassi e nel trattamento della neutropenia febbrile Introduzione Chemioterapia, neutropenia e G-CSFLa chemioterapia antiblastica, anche nell' era delle terapie target, resta il caposaldo del trattamento della maggioranza dei tumori solidi e delle neoplasie ematologiche. A fronte del beneficio clinico, alcuni effetti collaterali sono preminenti, in particolare la mielodepressione e, nell'ambito di questa, soprattutto la neutropenia. Il comparire di neutropenia durante il trattamento può portare una serie di ulteriori complicanze come la neutropenia febbrile e la riduzione della dose intensity, intesa come diminuzione della quantità di dose somministrata nell'unità di tempo. Da ciò deriva un possibile ridotto effetto dei farmaci sul controllo della malattia e quindi un peggiorato outcome [1]. Indubbiamente negli ultimi anni l'impiego in clinica...

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Differences in functional activity and antigen expression of granulocytes primed in vivo with filgrastim, lenograstim, or pegfilgrastim

Abstract: Our data suggest that granulocytes exposed to glycosylated G-CSF in vivo seem to resemble more closely their steady-state phenotype than after treatment with nonglycosylated and to lesser extent pegylated G-CSF.

Cited by 32 publications

References 59 publications

Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs

Comparison between filgrastim and lenograstim plus chemotherapy for mobilization of PBPCs

Enhanced biological effects of Phe140Asn, a novel human granulocyte colony-stimulating factor mutant, on HL60 cells

Appropriate administration of Granulocyte-Colony Stimulating Factors

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