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Immune-compromised state refers to a change of the host defense systems that confer an increased susceptibility to infection. Neutropenia remains the major defect of the defense systems predisposing to severe infections. Fever in a neutropenic patient should be considered a medical emergency as it has been demonstrated that a delay in specific therapy is associated with up to a 70% mortality rate (1). In this chapter, we present the medical approach to fever in neutropenic patients by analyzing the predisposing factors, pathogenesis, diagnosis, and treatment.


Fever in a neutropenic patient is usually defined as a single temperature of >38.3°C (101.3°F), or a sustained temperature >38°C (100.4°F) for more than 1 h. It has to be considered that neutropenic patients may experience clinical deterioration in the absence of fever and that concomitant steroid treatment may also conceal a fever.

Among neutropenic patients, two factors are associated with the increased risk of infection:

  • Neutrophil count. The risk increases when the neutrophil count is below 1 × 109/l. The risk of infection increases further in patients with neutrophil counts of less than 0.1 × 109/l neutrophils.

  • Duration of neutropenia. A low-neutrophil count and a protracted neutropenia (0.5 × 109/l for 10 days) are major risk factors for infection. A duration of neutropenia of more than 5 weeks is associated with an incidence of infection close to 100%.

Despite this, neutropenic patients remain a heterogeneous population that needs additional parameters that help to define the real risk of infection and tailor a more specific approach for each patient in this category. The risk factors for infection associated with neutropenia include advanced age, poor performance or nutritional status, low baseline and first-cycle nadir blood cell counts, and high-dose chemotherapy. Significant predictors for death, bacteremia, and length of hospital stay include advanced age, hematologic malignancies, disease burden, high fever, and low blood pressure on admission, pneumonia, and single or multiorgan dysfunction.


A number of predisposing factors other than neutropenia play a role in increasing the risk of infections in neutropenic patients with fever:

  • Chemotherapy

  • Intravenous or implanted devices

  • Hypogammaglobulinemia (i.e., chronic lymphocytic leukemia, multiple myeloma, splenectomy)

  • Defects in cell-mediated immunity (ALL, NHL, HD, therapy with fludarabine or alemtuzumab)

  • Glucocorticoid therapy

  • Disruption of normal anatomic structures

Chemotherapy not only affects the number of neutrophils but also impairs chemotaxis and phagocytosis. Either chemotherapy or radiotherapy-associated mucositis may affect the normal mucosal barrier, predisposing to bacteremia.

The existence of an impairment in neutrophil function preceding chemotherapy as in patients with myelodysplastic syndromes or in the presence of bone marrow failure due to tumor cell invasion predisposes to severe infection or death after chemotherapy (2).

Indwelling catheters and implanted devices pose a ...

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