Neutropenia

Neutropenia, defined as an absolute neutrophil count of less than 500 cells/^l, occurs frequently in cancer patients undergoing systemic chemotherapy. Among patients with genitourinary malignancies, this scenario is most common in patients with advanced TCC of the bladder. In this setting, the administration of MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) or GC (gemcitabine, cisplatin) chemotherapy leads to the development of grade 3 or 4 neutropenia (World Health Organization classification) in 80% and 43%-71% of patients, respectively (von der Masse et al. 2000). Although less frequent, neutropenia may also occur with conventional (bleomycin, etoposide, cisplatin) and salvage (ifosfamide-based) chemotherapy during the treatment of metastatic germ cell cancer (Bosl et al. 2005).

Neutrophils represent the first cellular component of the inflammatory response. As such, neutropenia poses significant risk for the development of infection. Both the degree and duration of neutropenia have been shown to correlate strongly with the incidence of serious infection (Bodeyetal. 1966). Numerous risk factors have been identified for the development of neutrope-nia and subsequent infection. Patient-specific risk factors include hematologic malignancy, advanced tumor stage, significant co-morbidities, poor performance status, and advanced age, while treatment-specific risk factors include chemotherapy type and dose intensity (Crawford et al. 2004). Incorporation of these risk factors into predictive models serves to guide prophylaxis and treatment recommendations against neutropenia (Lyman et al. 2005).

The inflammatory response to infection is severely weakened in the setting of neutropenia. Not only does this predispose to the development and rapid progression of infection, but it also lessens the associated signs and symptoms thereof. To prevent the development of infection and infection-related complications, it is essential that neutropenic cancer patients receive prompt evaluation and appropriate management. Antimicrobial prophylaxis for the prevention ofinfection is controversial. While clinicians are divided on its use, current guidelines recommend against the use of prophylactic antibiotics in neutropenic patients without fever, citing a lack of consistent reduction in mortality rates as well as concern over the emergence and propagation of drug-resistant bacteria and fungi (Hughes et al. 2002). An exception to this rule is found in patients considered to be at high risk for the development of Pneumocystis carinii pneumonitis. In these patients, prophylactic trimethoprim-sulfamethoxazole is recommended. Hematopoietic growth factors such as granulocyte colony-stimulating factor (filgrastim) or granulocyte-macrophage colony-stimulating factor (sargramostim) represent additional potential treatment options. When given as primary prophylaxis, these agents can reduce the incidence of febrile neutropenia by as much as 50% (Ozer et al. 2000). However, the American Society of Clinical Oncology (ASCO) does not recommend the routine use of prophylactic colony-stimulating factors in patients undergoing chemotherapy since no improvements in survival or response rate have been demonstrated with such practice (Ozer et al. 2000). Likewise, therapeutic colony-stimulating factor is not recommended as routine treatment for afebrile neutro-penic patients based on a demonstrated lack of clinical benefit. Finally, adjustments to the chemotherapy regimen may become necessary in some neutropenic patients. Although this allows for bone marrow recovery, it should be considered an option of last resort since lower cancer-specific survival is well documented among patients receiving less than full-dose chemotherapy (Lepage et al. 1993; Budman et al. 1998).

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