Colony stimulating factors

Information about Colony stimulating factors

Granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) are glycosylated polypeptides that induce an increase in the proliferation and maturation of white blood cells including neutrophils and monocytes-macrophages.  Recombinant forms of these colony stimulating factors are used to treat severe neutropenia in patients receiving cancer chemotherapy or undergoing hematopoietic cell transplantation.  Recombinant forms include filgrastim (G-CSF) and sargramostim (GM-CSF), both of which are commercially available for therapy of severe neutropenia and bone marrow failure. 

Liver toxicity of Colony stimulating factors

Neither filgrastim nor sargramostim have been linked to serum enzyme elevations during therapy or to clinically apparent liver injury.

Mechanism of action of Colony stimulating factors

Filgrastim (fil gra' stim) is a recombinant, non-glycosylated form of the 175 amino acid protein, granulocyte colony stimulating factor (G-CSF) that induces the proliferation and maturation of neutrophils.  G-CSF is normally produced by multiple cell types including monocytes, fibroblasts, macrophages and stromal cells.  It acts on specific receptors found on granulocyte progenitors and causes an increase in circulating neutrophils.  Recombinant filgrastim has been shown to increase total neutrophil counts and to protect, in part, against severe infections in patients with neutropenia for various causes.

Filgrastim

Filgrastim was approved for use in the United States in 1991, and current indications are for chemotherapy induced neutropenia, in hematopoietic cell transplantation after myeloablation and in congenital and cyclic neutropenias.  Filgrastim is also used in patients undergoing autologous peripheral blood progenitor (stem) cell collection.  Filgrastim is available as a solution in single use vials or prefilled syringes (300 and 600 mcg each) for subcutaneous or intravenous administration under the brand name Neupogen.  Dose regimens vary by indication (5 or 10 mcg/kg per day) and route of administration (intravenous or subcutaneous).  

Neulasta

A pegylated, long acting form of G-CSF (pegfilgrastim) became available in 2002 under the brand name Neulasta which can be given once weekly and has similar efficacy and safety as filgrastim.  The current formal indications for pegfilgrastim are limited to prevention of febrile neutropenia during myelosuppressive cancer chemotherapy for non-myeloid malignancies.  Pegfilgrastim is available in solution of 6 mg/0.6 mL in prefilled syringes.  The typical dose is 6 mg subcutaneously once per chemotherapy cycle.  Common side effects of filgrastim and pegfilgrastim include fever, musculoskeletal pain, rash, cough and shortness of breath.  Rare side effects include acute allergic reactions, splenic rupture and acute respiratory distress syndrome.

Sargramostim

Sargramostim (sar gra' moe stim) is a recombinant form of granulocyte-macrophage stimulating factor (GM-CSF) that stimulates the proliferation and maturation of neutrophils and macrophages.  Sargramostim is prepared in yeast (S. cerevisae) and is a 127 amino acid glycoprotein that is 98% identical to native, human GM-CSF.  Sargramostim increases the number and activity of circulating neutrophils and monocytes.  Sargramostim was approved in the United States in 1991 for use in patients with acute myelogenous leukemia after chemotherapy induced neutropenia.  Current indications also include support of patients undergoing hematopoietic cell transplantation as well as for patients undergoing autologous peripheral blood progenitor (stem) cell collection.  Sargramostim is available in liquid and lyophilized forms under the brand names Leukine and Prokine.  Sargramostim is given either intravenously or subcutaneously daily or three times weekly, the dose and regimen varying by indication.  Common side effects include fever, headache, fatigue, bone pain, nausea and weakness, but similar rates of these symptoms are reported with placebo or comparator therapies. Hematologic Agents Eculizumab, Emapalumab, Emicizumab, Lanadelumab, Ravulizumab

Hematologic Growth Factors

• Granulocyte colony stimulating factors
  • Filgrastim, Pegfilgrastim

• Granulocyte-Macrophage Colony Stimulating Factors
  • Sargramostim

• Erythropoiesis stimulating agents
  • Epoetin, Darbepoetin, Peginesatide

Thrombopoietin receptor agonists and Thrombopoiesis Stimulators

• • Avatrombopag, Eltrombopag, Fostamatinib, Lusutrombopag, Romiplostim, Oprelvekin (IL-11)

• Dailymed label info on Colony stimulating factors
• FDA Colony stimulating factors

Colony stimulating factors Resources
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