**5. Neutropenia**

side of the sinusoids, the special vascular structure of the bone marrow. The chemokine receptor CXCR4 is essential for the homing of stem cells and more mature neutrophils to the

Deletion of CXCR4 causes mature neutrophils to be released from the bone marrow into

The production of neutrophils is extensive, with 1 - 2 × 1011 cells being generated per day in a normal adult human. Granulocyte colony stimulating factor (G-CSF) is essential for tuning the production of neutrophils to meet the increased needs that occur during infections, but G-CSF is not absolutely required for granulocytopoiesis. Indeed, G-CSF null mice have approximately 25% residual granulocytopoiesis and still generate fully mature neutrophils [6]. The produc‐ tion of neutrophils is largely regulated by the rate of apoptosis of neutrophils in tissues. When macrophages and dendritic cells phagocytose apoptotic neutrophils in tissues, the production

Neutrophils are the body's first line of innate defense from micro-organismsand and inflam‐ mation. Neutrophils are able to bind to and ingest invading microorganisms such as bacteria, fungi, germs, or any foreign body in the blood by a process known as phagocytosis, most likely due to their defensive and/or phagocytic process is by their ability to release lytic enzymes

Neutrophils cells directly recognize surface-bound or freely secreted molecules produced by bacteria (i.e., pathogen-derived molecules), including peptidoglycan, lipoproteins, lipoteicho‐ ic acid, lipopolysaccharide (LPS), CpG-containing DNA, and flagellin. These pathogenderived molecules, known as pathogen-associated molecular patterns, interact directly with a number of pattern-recognition receptors expressed on the cell surface of neutrophil cell. Pattern-recognition receptors play a role in the recognition of microbes by neutrophils, and the efficiency of phagocytosis by neutrophils is markedly enhanced if microbes are opsonized

Neutrophils have receptors on their surface that help them to contact and bind to tissues and to the vascular endothelium near sites of infection or inflammation [2] and they are the first cells that migrate to the site of invasion or inflammation to start the clearance of infectious particles. In the events of invading foreign threat, they also send warning signals to other innate

Thus the migration of neutrophils from the blood circulation to surroundings tissues is

During the process of migration to site of invasive, neutrophils need to cross the vessel wall (transmigration). This takes place largely at postcapillary venules, where the vessel wall is rather thin, and the diameter of the vessel is sufficiently small that the neutrophils can make

from their granules and to produce reactive oxygen intermediates (ROI) [2, 3, 4, 8].

with serum host proteins, such as complement and/or antibody [9].

circulation without affecting the life-span of circulating neutrophils [6, 7].

bone marrow [6].

202 Updates on Cancer Treatment

of interleukin 23 (IL-23) is reduced [6].

**3. The role of neutrophils**

immune cells [1].

considered key in triggering host defense.

Neutropenia is defined as a decrease in the absolute number of neutrophils in the blood. Clinically, neutropenia is defined as a decrease in the absolute neutrophil count (ANC) of more than two standard deviations below the normal range. Therefore, the patient is considered neutropenic when the ANC is lower than 1500 cells/µl (the normal level) [2, 3, 5, 13, 14]. An ANC above 1000 cells/µl will still confer normal protection against infection; therefore mild neutropenia is defined as an ANC 500 - 1000 cells/µl. There is a significant increase in the incidence of serious infection once ANC falls below 500 cells/µl, and moderate neutropenia is defined as an ANC of 200 - 500 cells/µl [2, 3, 13]. When ANC falls below 200 cells/µl it is defined as severe neutropenia. This condition is very serious and requires the patient to be admitted to the hospital and treated with antibiotics [3, 13], and patients with an ANC below 100 cells/ µl are at the highest risk of infection. Hundred percent of the patients with ANC < 100 cells/µl lasting 3 weeks or more develop documented infection.

Neutropenia is usually diagnosed by a complete blood count (CBC) or full blood count (FBC). If the results show a low ANC then these tests are repeated [15]. If the repeated test shows the same results, a bone marrow biopsy is carried out to confirm the diagnosis. Bone marrow aspirate is taken from two sites, one from the middle of the bone and one from the solid, bonier part of the bone, usually from the large pelvic bone, the ilium, or the sternum [15].

Febrile neutropenia (i.e., neutropenia with fever) is mostly associated with chemotherapy, but it may also occur after irradiation of the bone marrow. In this chapter, the term febrile neutropenia is usually used to describe the occurrence of neutropenia (body temperature ≥38.3°C or oral temperature ≥38°C for more than hour) and an ANC of ≤ 500 cells/µl at the time of fever, or in the following 48 hours [2, 14, 15, 16, 17, 18].
