Leukopenia is a condition of reduced white blood cells (leukocytes). Neutrophils, the most abundant leukocytes, are involved in killing pathogens; thus, leukopenia is associated with an increased risk of bacterial and fungal infections (Merck 2006, 2012a).
Causes and Risk Factors
The most common causes of leukopenia are recent infection, chemotherapy, radiation therapy, and HIV (Merck 2012a), but it can also be caused by certain medications such as the antipsychotic clozapine (Clozaril®) and the antibiotic minocycline (Minocin®) (Ahmed 2007; Latif 2012). Leukopenia is a common side effect of anti-cancer drugs, as such drugs attack rapidly dividing cells (including neutrophils) (Merck 2012a). Similar to anemia, an enlarged spleen can also cause leukopenia by increasing the clearance/destruction of leukocytes (He 2011). The most common type of neutropenia (ie, an abnormally low number of neutrophils) is drug-induced; for instance, chloramphenicol (an antibacterial drug) is associated with reduced neutrophil counts and the induction of aplastic anemia (Paez 2008).
Treatment of neutropenia with fever depends on the overall clinical profile of the patient. Pharmaceuticals that may be employed include antibiotics such as ciprofloxacin (Cipro®), amoxicillin/clavulanate (Augmentin®), ceftazidime (Fortaz®), piperacillin/tazobactam (Zosyn®), and vancomycin (Vancocin®) (Macartney 2007; Freifeld 2011). The goal of antimicrobial therapy is to prevent further infection, since neutropenia is associated with significantly increased susceptibility to pathogens (Friefeld 2011).
In certain conditions where neutropenia is expected, such as chemotherapy, granulocyte colony-stimulating factors (eg, filgrastim [Neupogen®]) and/or granulocyte macrophage colony-stimulating factors (eg, sargramostim [Leukine®]) can be used as a preventive measure (Renner 2012). These drugs stimulate the bone marrow to produce more white blood cells, including neutrophils, and importantly, they allow patients to continue chemotherapy without having to reduce the dose due to side effects, thereby improving therapeutic outcomes (Renner 2012; Palumbo 2012). Furthermore, the European Organization for Research and Treatment of Cancer has recommended these agents be considered in all patients prior to the initiation of chemotherapy, particularly at-risk patients (eg, elderly patients or patients with low neutrophil counts) or those who have already experienced neutropenia with fever after previous courses of therapy (Aapro 2011).
Empegfilgrastim. Within 24 hours of receiving chemotherapy, the granulocyte-stimulating factor filgrastim is administered daily by subcutaneous injection for 2 weeks. Conversely, empegfilgrastim (Extimia®) is a derivative of filgrastim that has been molecularly modified to significantly extend the time it remains biologically active, thus necessitating only one dose. This drug and dosing regimen has demonstrated efficacy in non-human primates after high-dose radiation therapy (Farese 2012) and, as of this writing, Extimia® is being evaluated in an open-label randomized phase II clinical study (BCD-017-2), which is expected to conclude in 2013 (ClinicalTrials.gov 2012a).