Granulocyte Colony-Stimulating Factors: Use, Administration, Adverse Effects
G-CSFs are a bone-marrow–derived growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells.
The immune system consists of 2 types of immunity: innate and adaptive. Innate immunity is described as the immune system that initially presents and is an immediate response. It works by providing the first line of defense from infectious processes. The adaptive immune system is more complex and slower to respond. It is responsible for recognizing foreign antigenic substances. The adaptive immune system is further subdivided into humoral and cellular immunity.1 This article focuses on innate immunity because it plays an important role in host recognition of and response to bacterial, fungal, and parasitic pathogens.
Innate immunity is composed mostly of phagocytes in the granulocyte and monocyte lines, which include polymorphonuclear leuckocytes, circulating monocytes, and tissue-based macrophages.
Neutrophils are phagocytes. They ingest and kill invading bacteria, releasing cytotoxic, chemotactic, and inflammatory mediators at sites of infection.2 The development of cytokines to enhance phagocytic function and alter host defense has been ongoing since the mid-1960s. Four different cytokines have been described: granulocyte colony stimulating factor, granulocyte/macrophage colony stimulating factor, macrophage colony stimulating factor, and interferon. For this paper, I will focus on granulocyte colony-stimulating factors (G-CSFs), such as filgrastim and derivative products including pegfilgrastim and biosimilars.3
How G-CSFs Work and Their Use
G-CSFs, in general, are a bone-marrow–derived growth factor produced by monocytes, macrophages, fibroblasts, and endothelial cells. Initially, G-CSFs were described as a hematopoietic glycoprotein that regulates cell cycle activation, proliferation, terminal maturation, and survival of the myeloid lineage in the bone-marrow–producing mature polymorphonuclear cells (neutrophils). These growth factors are stimulated in the bone marrow to produce neutrophils.3 G-CSF binds to the cell surface of hematopoietic cells in the bone marrow and stimulates neutrophil progenitor cell proliferation and differentiation. This mechanism of action helps speed neutrophil growth and maturity, increasing the number of mature neutrophils that are released into the circulation.4
The most common clinical uses for G-CSFs in patients with lymphoma is to accelerate neutrophil recovery after induction or high-dose chemotherapy and for bone marrow/peripheral stem cell transplantation. Patients with lymphoma who are receiving chemotherapy, especially high-dose immunosuppressive therapy, are at risk for developing neutropenia.