G-CSF and GM-CSF in Neutropenia

Abstract

G-CSF and GM-CSF are used widely to promote the production of granulocytes or APCs. The U.S. Food and Drug Administration approved G-CSF (filgrastim) for the treatment of congenital and acquired neutropenias and for mobilization of peripheral hematopoietic progenitor cells for stem cell transplantation. A polyethylene glycol-modified form of G-CSF is approved for the treatment of neutropenias. Clinically significant neutropenia, rendering an individual immunocompromised, occurs when their number is <1500/μl. Current guidelines recommend their use when the risk for febrile neutropenia is >20%. GM-CSF (sargramostim) is approved for neutropenia associated with stem cell transplantation. Because of its promotion of APC function, GM-CSF is being evaluated as an immunostimulatory adjuvant in a number of clinical trials. More than 20 million persons have benefited worldwide, and >$5 billion in sales occur annually in the United States.

Figure 1

A. The scheme of hematopoiesis from the multipotential hematopoietic stem cell to fully differentiated cell types. Principal cytokines that determine differentiation patterns in red. Epo, Erythropoietin; FLT-3 ligand, FMS-like tyrosine kinase 3 ligand; G-CSF, Granulocyte-colony stimulating factor; GM-CSF, Granulocyte Macrophage-colony stimulating factor; IL, Interleukin; M-CSF, Macrophage-colony stimulating factor; SCF, Stem Cell Factor; SDF-1, Stromal cell-derived factor-1; TGFβ, Transforming growth factor beta; TNFα, Tumour necrosis factor-alpha; Tpo, Thrombopoietin; B. The stages of granulopoiesis from myeloblast to the mature granulocyte. During neutrophil maturation, which is driven primarily by G-CSF, granulocytic cells change shape, acquire primary and specific granules, and undergo nuclear condensation.

Figure 1

A. The scheme of hematopoiesis from the multipotential hematopoietic stem cell to fully differentiated cell types. Principal cytokines that determine differentiation patterns in red. Epo, Erythropoietin; FLT-3 ligand, FMS-like tyrosine kinase 3 ligand; G-CSF, Granulocyte-colony stimulating factor; GM-CSF, Granulocyte Macrophage-colony stimulating factor; IL, Interleukin; M-CSF, Macrophage-colony stimulating factor; SCF, Stem Cell Factor; SDF-1, Stromal cell-derived factor-1; TGFβ, Transforming growth factor beta; TNFα, Tumour necrosis factor-alpha; Tpo, Thrombopoietin; B. The stages of granulopoiesis from myeloblast to the mature granulocyte. During neutrophil maturation, which is driven primarily by G-CSF, granulocytic cells change shape, acquire primary and specific granules, and undergo nuclear condensation.