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Neutropenic Complications of Chemotherapy
Introduction
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Neutrophils, eosinophils, and basophils are a subset of white blood cells characterized by the presence of granules and collectively referred to as granulocytes. Granulocytopenia is a decrease in the absolute count of these three cell lines while neutropenia is a decrease in only the absolute neutrophil count (ANC). However, for practical purposes the terms granulocytopenia and neutropenia are often used interchangeably.
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It is important to understand normal physiology in order to understand neutropenia and its complications. Most neutrophils reside in the bone marrow in mitotic (myeloblasts, promyelocytes, myelocytes) and postmitotic (metamyelocytes, bands, and then neutrophils) stages. Of the neutrophils in the circulation, an equal proportion make up the marginal and the nonmarginal pool. From the circulation, neutrophils enter tissue as a result of proinflammatory trafficking cytokines. Neutropenia is a reduction in the nonmarginal pool of neutrophils which constitute only 4% to 5% of total neutrophil stores.
Neutropenia is defined as an absolute neutrophil count (ANC) of less than 1500 cells/µL; ANC of less than 1000 cells/µL is considered moderate neutropenia and ANC of less than 500 cells/µL is considered severe neutropenia. The risk of infection is greatest with severe neutropenia.
Etiology of Neutropenia
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Neutropenia is a common complication seen in various malignant conditions. There are many contributing factors that should be considered in patients with malignancy. Table 2.1 describes causes of neutropenia commonly seen in patients with malignancy. Although neutropenia is the most common dose limiting toxicity (DLT) of chemotherapy, it is important to consider the differential diagnosis to determine the appropriate management for each patient.
TABLE 2.1Causes of Neutropenia in Cancer PatientsCauses of Neutropenia in Malignancy Mechanism Chemotherapy ( the chemotherapy regimen remains the strongest determinant in the likelihood of developing neutropenia ) Myelosuppressive effects due to cytotoxicity Chronic lymphoproliferative disorders – natural killer cell lymphomas (large granular lymphocytic leukemia), hairy cell leukemia, and chronic lymphocytic leukemia (CLL) Bone marrow infiltration Radiation Cytotoxic Effects Autoimmune conditions: Systemic lupus erythematosus (SLE), aplastic anemia, Crohn's disease Presence of antineutrophil antibodies Rheumatoid arthritis (Felty's syndrome) Hypersplenism Granulomatous infections Bone marrow infiltration Viral infections (e.g., CMV, EBV, HIV) Bone marrow suppression Parasitic infections (e.g., malaria) Hypersplenism, multifactorial Bacterial infections (e.g., typhoid, tuberculosis) Multifactorial Hemophagocytic lymphohistiocytosis (HLH) Infiltration of bone marrow, hypersplenism Antibiotic-induced isolated neutropenia (e.g., quinidine, hydralazine, β-lactams) Maturation arrest of myeloid lineage Benign ethnic neutropenia (BEN; also known as constitutional neutropenia) Inherited predisposition Cyclic neutropenia (21-day cycling of neutrophils) Inherited (autosomal dominant, ELA2 gene) and acquired causes CMV, Cytomegalovirus; EBV, Epstein-Barr virus. - ■
There are several ways in which chemotherapy predisposes to infections. While neutropenia is an important etiology, chemotherapy can also impair physical barriers created by mucosal surfaces, the first line of defense against infections. Classic signs of inflammation including dolor (pain), calor (heat), rubor (redness), tumor (swelling), and functio laesa (loss of function) may be dampened in such patients due to blunting of the function of neutrophils. Thus increasing the chance of infections to be missed. Fever is usually the only sign of infection in neutropenic infections and thus warrants special vigilance.
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