Uses of Colony-Stimulating Factors

The CSFs prevent chemotherapy-induced neutropenia. They stimulate hematopoiesis in marrow failure. The CSFs promote cell differentiation, assist in marrow transplantation, stimulate monocyte anticancer effects and augment effector cell function. 

G-CSF is a glycoprotein produced by macrophages, endothelium and various leukocytes. It stimulates the bone marrow to produce granulocytes and stem cells and then directs their migration from the bone marrow to the peripheral blood. G-CSF is a growth factor for the proliferation, differentiation, effector function and survival of neutrophils. The gene for G-CSF is located on chromosome 17, locus qll.2-ql2. 

G-CSF mobilizes bone marrow-derived cells into the bloodstream. These stem cells can migrate to ischemic myocardium and differentiate into cardiomyocytes, smooth muscle cells and endothelial cells. They may also induce metalloproteinases and vascular endothelial growth factor and thus play a role in tissue healing. Furthermore, G-CSF induces proliferation and enhanced survival of cardiomyocytes. This is accomplished via activation of G-CSF receptors in myocardium. G-CSF in association with TGF- 3 and collagen enhances ventricular expansion in the infarcted area. 

G-CSF activates neutrophils, transforming them into cells capable of respiratory burst and release of secretory granules. It also modulates the expression of adhesion molecules on neutrophils as well as CD1 lb/CD18 and plasma elastase antigen levels. G-CSF induces proliferation of endothelial cells, phagocytic activity of neutrophils, reactive oxygen intermediate production by neutrophils and antibody-dependent cellular toxicity by neutrophils. 

Filgrastim is administered by intravenous infusion or subcutaneous injection. The doses given are 1-20 pg/kg per day over at least a 30-min period. Generally a dose of 5 pg/kg is used in patients receiving chemotherapy for 14-21 days or longer. The half-life of the drug is 3.5 h. The side effects include bone pain, local skin reactions and rarely cutaneous vasculitis. 

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There is much controversy regarding the routine use of colony-stimulating factors (e.g., G-CSF and GM-CSF) in neutropenic patients. Even though several clinical trials have shown... 

There has been a great deal of interest in the use of colony-stimulating factors to treat MDS. GM-CSF and G-CSF, which have been used in clinical trials, offer a potential dual benefit. Firstly, they can affect neutrophil development in the bone marrow, and so can improve the neutropenia that is associated with these disorders. Secondly, they have the potential to increase or repair the function of circulating neutrophils. Indeed, there are some reports to indicate that these CSFs can result in enhanced function of peripheral blood neutrophils in these patients. Most patients show improvements in neutrophil counts after GM-CSF or G-CSF administration. In some cases, this has been associated with a decrease in the number of infective episodes. 

After a meticulous review of the biomedical literature, the panel concluded that routine use of colony-stimulating factors for primary prophylaxis of febrile neutropenia in previously untreated patients is not justified by existing data. There is evidence, however, that colony-stimulation factor administration can decrease the probability of febrile neutropenia in subsequent cycles of chemotherapy after a documented occurrence in an earlier cycle. However, dose reduction after a severe episode, rather than administration of colony-stimulating factors, should be considered as a primary therapeutic option. In the absence of clinical evidence or other compelling reasons to maintain chemotherapy dose intensity, physicians should consider chemotherapy dose reduction... 

Andres E, Maloisel F, Ruellan A. Use of colony-stimulating factors for the treatment of antithyroid drug-induced agranulocytosis a retrospective study in twelve patients. Thyroid 2000 10(1) 103. 

Consider consultation with hematologist and radiation experts to determine dosimetry, prognosis, use of colony stimulating factors, stem cell transfusion, and so forth. 

Lyman GH, Kuderer N, Agboola O, Balducci L. Evidence-based use of colony-stimulating factors in elderly cancer patients. Cancer Control 2003 10 487-99. 

Schaison G, Eden OB, Henze G, Kamps WA, LocateUi F, Ninane J, Ortega J, Rukonen P, Wagner HP. Recommendations on the use of colony-stimulating factors in children conclusions of a European panel. Eur J Pediatr 1998 157(12) 955-66. 

USE OF COLONY-STIMULATING FACTORS IN ACUTE MYELOID LEUKEMIA... 

Sasaki, K. et al. 2008. Enhancement of tendon-bone osteointegration of anterior cruciate ligament graft using granulocyte colony-stimulating factor. Am. /. Sports Med. 36 1519-1527. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Neutropenia associated with interferon or pegylated interferon therapy is defined as an absolute neutrophil count (ANC) of less than 1000 cells/mm3 in rare cases, an ANC less than 500 cells/mm3 maybe observed. The neutropenia is more common and in some cases more severe with pegylated interferon than with unmodified interferon. Neutropenia usually occurs within the first 2 weeks after initiating either formulation of interferon, with the WBC count stabilizing by week four or six. The neutropenia is reversible upon discontinuing therapy. Granulocyte colony-stimulating factor has been used as an adjunctive therapy for interferon-induced neutropenia in hepatitis patients.44... 

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