Clinical application of colonystimulating factors

Several CSF preparations have gained regulatory approval (Table 10.2). G-CSF and GM-CSF have proven useful in the treatment of neutropenia. All three CSF types are (or are likely to be) useful also in the treatment of infectious diseases, some forms of cancer and the management of bone marrow transplants, as they stimulate the differentiation/activation of white blood cell types most affected by such conditions.

GSM-CSF

GSM-CSF

Cell membrane

Cell cytoplasm

Figure 10.2 The GM-CSF receptor. Ligand binding appears to promote the phosphorylation of various cytoplasmic polypeptide substrates (at least in part via an associated JAK2), leading to signal transduction

Neutropenia is a condition characterized by a decrease in blood neutrophil count below 1.5 X 109 cells per litre; a normal blood count is (2.0-7.5) X 109 cells per litre. Its clinical symptoms include the occurrence of frequent and usually serious infections, often requiring hospitalization. Neutropenia may be caused by a number of factors (Table 10.6), at least some of which are responsive to CSF treatment. Particularly noteworthy is neutropenia triggered by administration of chemothera-peutic drugs to cancer patients. Chemotherapeutic agents (e.g. cyclophosphamide, doxorubicin and methotrexate), when administered at therapeutically effective doses, often induce the destruction of stem cells and/or compromise stem cell differentiation.

Filgrastim is a recombinant human G-CSF (produced in E. coli), approved for chemotherapy-induced neutropenia (Table 10.2 and Box 10.1). Neulasta is the tradename given to a PEGylated form of filgrastim approved for general medical use in the USA in 2002 (Table 10.2). Manufacture of this product entails covalent attachment of an activated monomethoxypolyethylene glycol molecule to the N-terminal methionyl residue of filgrastim. The product is formulated in the presence of acetate buffer, sorbitol and polysorbate and is presented in pre-filled syringes for s.c. injection. As in the case of PEGylated interferons (Chapter 8), the rationale for PEGylation is to increase the drug's plasma half-life, thereby reducing the frequency of injections required.

Genetic (particularly in black populations)

Severe bacterial infection

Severe sepsis

Severe viral infection

Aplastic anaemiaa

Acute leukaemia

Hodgkin's/non-Hodgkin's lymphoma Various drugs, especially anti-cancer drugs Autoimmune neutropenia

Table 10.6 Some causes of neutropenia

"Aplastic anaemia describes bone marrow failure, characterized by serious reduction in the number of stem cells present.

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment