Recombinant Granulocyte Colony-Stimulating Factor (rG-CSF)

Abstract

Recombinant granulocyte colony-stimulating factor (rG-CSF) is a glycoprotein hormone which has been produced in mammalian cells and, in a nonglycosylated form, in the bacterium Escherichia coli through recombinant DNA technology. It stimulates proliferation, differentiation and activation of cells of the neutrophil-granulocyte lineage and has been investigated as therapy for patients with various neutropenic conditions, both iatrogenic and disease related. rG-CSF is well tolerated, the most frequently reported adverse effect being mild to moderate bone pain. A major use for rG-CSF therapy will be in ameliorating the neutropenia which follows cytoreductive chemotherapy. rG-CSF accelerates neutrophil recovery after chemotherapy, leading to a reduction in duration of the neutropenic phase. Consequently, infection rate is diminished, as is the associated usage of antibiotics and duration of hospitalisation. The implications are that rG-CSF may allow increased dose intensity and stricter adherence to chemotherapy schedules. The increase in neutrophils produced by rG-CSF renders it a useful treatment for conditions such as congenital, acquired and cyclic neutropenias for which current therapy is not very successful. rG-CSF may be an effective therapy in myelodysplasia, although there is concern about acceleration of the possible rate of conversion of this disease to acute myelogenous leukaemia. It is also likely that rG-CSF will be useful in accelerating the recovery of transplanted bone marrow in patients with leukaemia, lymphoma and solid tumour. Furthermore, there is great potential for expansion of the role of rG-CSF as monotherapy or in combination regimens with other cell factors in various haematological disorders such as aplastic anaemia. In summary, while many aspects of its use remain to be clarified, rG-CSF must be seen as an exciting advance in therapeutics. It should rapidly find an important place as an adjunct to cancer chemotherapy, and also appears to have substantial potential in a number of other neutropenic conditions which are currently difficult to treat.

Ex vivo neutrophil function in response to three different doses of glycosylated rHuG‐CSF (Lenograstim)

“…In both neutropenic and non-neutropenic subjects, G-CSF administration has been extensively shown to rapidly elevate circulating polymorphonuclear leucocyte (PMN) counts in a dose-dependent fashion (Hollingshead & Goa, 1991). The present study also shows that the administration of 2 .…”

“…In both neutropenic and nonneutropenic subjects, G-CSF has been found to rapidly increase the number of circulating PMN in a dose-dependent fashion and has therefore been investigated as therapy for patients with various neutropenic conditions (Bensinger et al, 1993;Hollingshead & Goa, 1991). G-CSF has also been shown to potently stimulate or enhance certain effector functions of mature human PMN, these being properties that are primarily related to hose defence against invading pathogens (Demitri & Griffin, 1991).…”

Granulocyte Colony-Stimulating Factor for Neutropenia Secondary to Ticlopidine

“…Moreover, all three became afebrile within 24 h after initiation of G-CSF treatment, although the ANCs were not substantially in creased in two of them at that time. This might support a stimulatory effect on the mature circulating neutrophils, as has been pointed out by other authors [6,7]. No patient suffered any adverse reaction.…”

“…It has a selective effect on the granulocytic precursors resulting in an apparent rise of circulating neutrophils [5][6][7]. Al though, there is not much experience with G-CSF as a treatment for toxic neutropenias [8][9][10], the reported re sults, all of them anecdotal, are promising.…”

Recombinant Human Granulocyte Colony-Stimulating Factor Reverts Vascular Dysfunction

“…This hematopoietic factor does not show species boundary and therefore rh G-CSF has been used in experimental animals [11], A recent report has suggested that rh G-CSF possesses beneficial effects on survival and hemodynamics of ani mals subjected to septic shock. Flowever, the beneficial effects of rh G-CSF in this experimental model are ascribed to its multiple biological effects on cells of neu trophilic lineage.…”