Effect of Granulocyte Colony Stimulating Factor on Neutropenia Induced by Cytotoxic Chemotherapy

Morstyn, George; Campbell, Lynda J.; Souza, LM; Nk, Alton; Keech, John; Green, M; Sheridan, William; Metcalf, Donald; Fox, R. H.

doi:10.1016/s0140-6736(88)91475-4

Cited by 679 publications

(188 citation statements)

References 21 publications

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“…The reason for this initial decrease is unclear and requires further investigation, but it might be related to migration of circulating neutrophils into tissues or to increased adherence of neutrophils to endothelium. Similar findings have been recently reported by Morstyn et al (1988) following rhG-CSF given by short intravenous infusion. The subsequent rise in peripheral neutrophils produced by rhG-CSF is probably due to an increase in the influx of cells from the bone marrow (both mature and de novo granulocytes).…”

Section: Discussionsupporting

confidence: 91%

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients

Bronchud

Potter²,

Morgenstern³

et al. 1988

Br J Cancer

178

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Summary Twelve patients with small cell lung cancer were treated with recombinant human granulocyte colony-stimulating factor, rhG-CSF, given by continuous infusion at doses ranging from 1 to 40 ig kg-'day-'. Patients received the rhG-CSF before the start of intensive chemotherapy and after alternate cycles of chemotherapy. Several in vitro assays were performed using peripheral blood neutrophils and marrow progenitor cells collected from patients prior to and after infusion of the growth factor. Peripheral blood neutrophils were tested for mobility and phagocytic activity. In addition, in vitro clonogenic assays of marrow haemopoietic progenitor cells and analysis of bone marrow trephines and aspirates were carried out. We found that rhG-CSF in vivo has at least two main effects: (a) an early fall in peripheral neutrophils, within the first hour, followed by a rapid influx of mature neutrophils into the circulatory pool; (b) stimulation of proliferation and differentiation of neutrophil precursors in the bone marrow. Neutrophils released into the circulation were normal in tests of their mobility and phagocytic activity.

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Section: Discussionsupporting

confidence: 91%

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients

Bronchud

Potter²,

Morgenstern³

et al. 1988

Br J Cancer

178

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“…The circulating granulocytes are functionally 'primed' in vivo and demonstrate enhanced phagocytosis and killing activity (Welte et al, 1987). Human studies demonstrate a similar rapid and marked rise in the neutrophil count with only a minor rise in the monocyte and lymphocyte numbers and with no change in the eosinophil or platelet counts (Bronchud et al, 1987;Morstyn et al, 1988).…”

mentioning

confidence: 88%

Clinical significance of the haemopoietic growth factors

Devereux

Linch²

1989

Br J Cancer

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“…The severe neutropenia and thrombocytopenia can result in severe clinical consequences such as sepsis and hemorrhage, respectively, which are major causes of death during myelosuppression. Administration of recombinant human (rHu) G-CSF to patients after cancer chemotherapy can reduce the duration and severity of neutropenia with resultant sepsis [2,3]. On the other hand, platelet transfusion has been only supportive care for reduction of the duration and severity of thrombocytopenia after cancer chemotherapy, but this care is usually accompanied by complications such as alloimmunization [4].…”

Section: Introductionmentioning

confidence: 99%

Effects of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor on Thrombocytopenia Induced by a New Myelosuppressive Chemotherapy Regimen in Mice

Akahori¹,

Shibuya²,

Ozai³

et al. 1996

STEM CELLS

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Abstract. Thrombopoietin, the endogenous c-Mpl ligand, is a novel lineage-specific hematopoietic factor that plays a pivotal role in the regulation of megakaryocytopoiesis and thrombopoiesis. In this study, we examined the effects of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a truncated molecule of recombinant human c-mpl ligand derivatized with polyethylene glycol, on myelosuppressive chemotherapy-induced thrombocytopenia in mice. We developed a new murine model of thrombocytopenia induced by I.V. injections of mitomycin C (MMC) for two consecutive days. In control mice, platelet counts began to decrease on day 6, reached a nadir of less than 5% of basal level on day 14, and could not recover to basal level by day 26. Administration of PEG-rHuMGDF greatly enhanced recovery of the number of megakaryocyte progenitor cells and the megakaryocytes in bone marrow, and markedly reduced the severity of thrombocytopenia; it also accelerated platelet recovery in a dose-dependent manner in myelosuppressed mice. Mice receiving consecutive administration of higher doses of PEG-rHuMGDF showed no thrombocytopenia but rather had platelet counts being increased over basal level. Although absolute neutrophil counts and red cell counts also were decreased following MMC treatment, administration of PEG-rHuMGDF also improved neutropenia and anemia. Administration of PEGrHuMGDF on alternate days or once a week after chemotherapy was almost as effective as consecutive administration in improving thrombocytopenia. Combined administration of PEGrHuMGDF and rHuG-CSF had an addictive effect on improvement of thrombocytopenia and neutropenia. These results suggest that PEGrHuMGDF is a therapeutically effective agent in the treatment of thrombocytopenia associated with chemotherapy.

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Effect of Granulocyte Colony Stimulating Factor on Neutropenia Induced by Cytotoxic Chemotherapy

Cited by 679 publications

References 21 publications

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients

In vitro and in vivo analysis of the effects of recombinant human granulocyte colony-stimulating factor in patients

Clinical significance of the haemopoietic growth factors

Effects of Pegylated Recombinant Human Megakaryocyte Growth and Development Factor on Thrombocytopenia Induced by a New Myelosuppressive Chemotherapy Regimen in Mice

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