Additional Risk Factors for Febrile Neutropenia

A number of efforts to identify risk factors for the occurrence of FN or its consequences in patients with established FN have been reported. A systematic review has been completed of published studies of risk models for FN and its consequences (51). Nearly every study of risk factors for neutropenic complications in patients receiving cancer chemotherapy has identified increasing age as a significant independent predic-

Days to first FN episode

Fig. 6. Hazard plot of the time in days to the first episode of febrile neutropenia (FN) in 577 patients with non-Hodgkin's lymphoma treated with CHOP chemotherapy stratified by age 65 yr and over vs <65 yr (p = 0.0002). Modified from ref. 49.

Days to first FN episode

Fig. 6. Hazard plot of the time in days to the first episode of febrile neutropenia (FN) in 577 patients with non-Hodgkin's lymphoma treated with CHOP chemotherapy stratified by age 65 yr and over vs <65 yr (p = 0.0002). Modified from ref. 49.

tor of severe neutropenia or serious medical consequences of FN, including death (52). As noted above, increasing age was a significant independent predictor in a multivariate model of risk of FN across a number of adjuvant breast cancer treatment regimens among approx 20,000 women studied retrospectively in the United States (48). The elderly were more likely to experience significant reductions in dose intensity relative to either target dose intensity or published reference standards with these regimens. Patients aged >65 yr experienced nearly twice the rate of reduced dose intensity <85% in multivariate analyses after adjustment for the type of regimen used. In patients receiving CHOP for NHL, the study by Lyman et al. (49) reported a doubling of the hazard rate of FN in patients aged >65 yr, most of which occurred during the first cycle of therapy (Fig. 6). Similar analyses have been undertaken in women receiving adjuvant chemotherapy for ESBC (53). Silber and colleagues (54) previously developed and independently validated a risk model for neutropenic complications in the adjuvant ESBC setting based on a retrospective analysis. The nadir absolute neutrophil count (ANC) during the first cycle was the most predictive factor for future neu-tropenic events likely to reduce treatment dose intensity.

This approach was studied prospectively in a clinical trial of 729 women started on adjuvant chemotherapy for ESBC with or without growth factor support determined on the basis of the first-cycle ANC nadir (55). If the first-cycle ANC was <0.5 x 109/L, women were given prophylactic rHuG-CSF for all subsequent cycles, whereas all other patients received growth factor support only if a neutropenic event actually occurred. In further analysis of these data, Agboola et al. (56) found that pretreatment

Fig. 7. Bar graph displaying the cumulative proportion of patients with any subsequent neutropenic complication (NC) (febrile neutropenia [FN], dose reduction, or treatment delay) or FN alone based on a composite risk score age >65 yr or first cycle events including FN, absolute neutrophil count (ANC) < 5 X 109/L or a hemoglobin (Hb) decrease > 1 g/dL (p < 0.001) (56).

Fig. 7. Bar graph displaying the cumulative proportion of patients with any subsequent neutropenic complication (NC) (febrile neutropenia [FN], dose reduction, or treatment delay) or FN alone based on a composite risk score age >65 yr or first cycle events including FN, absolute neutrophil count (ANC) < 5 X 109/L or a hemoglobin (Hb) decrease > 1 g/dL (p < 0.001) (56).

factors predictive of first-cycle hematologic toxicity included age > 65 yr, white race, use of an anthracycline-containing regimen, body-surface area <2 m2, and low baseline ANC. Significant predictors of subsequent neutropenic complications including FN included age >65 yr and first-cycle events including ANC nadir, FN, and a decrease in Hb by >1 g/dL (Fig. 7).

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