Granulocyte Colony Stimulating Factor

CLL patients treated with fludarabine have been reported to have a significant incidence of severe infections (i.e., sepsis or pneumonia), especially in patients with advanced-stage disease or those who were pretreated (37). The incidence of severe infections ranged from 12% in previously untreated early-stage patients to 54% in previously treated advanced-stage patients. Grade 3 and 4 neutropenia were frequently reported and resulted in delays in therapy for approx 50% of the patients treated with fludarabine.

Table 5

Comparison of Therapy Delays Between Filgrastim-Treated and Historical Control Patients

Table 5

Comparison of Therapy Delays Between Filgrastim-Treated and Historical Control Patients

Course days

% of patients

p Value

Fludarabine + filgrastim

Historical control













Data from ref. 38.

Data from ref. 38.

In a phase 2 trial, 25 patients with CLL were enrolled in a study of fludarabine 30 mg/m2 iv for 30 min each day for 5 d, repeated every 4 wk. In addition, rHuG-CSF (filgrastim) was administered at 5 ^g/kg/d sc starting on d 6 and continuing until an absolute granulocyte count (AGC) of 10 x 109/L. Prophylactic antibiotics were not administered. Data from these 25 patients with CLL were compared with data from an historical control group of 145 CLL patients (previously treated Rai stage III and IV) who received single-agent fludarabine or fludarabine and oral prednisone at a dose of 30 mg/m2 daily for 5 d per month. Response rates and overall toxic effects were similar among the historical control group patients except for an increase in Listeria monocytogenes sepsis and/or Pneumocystis carinii pneumonia that occurred only in patients given the combination therapy (37).

No difference was seen in the response rate or in the median time to disease progression between the treatment group and the historical control group (38). A statistically significantly difference with less grade 3 and 4 neutropenia was seen in the treatment groups compared with historical controls for all cycles of therapy (nadir < 1.0 x 109/L, 45% vs 79%, p = 0.002; nadir < 0.5 x 109/L, 15% vs 63%, p = 0.000) as well as for each individual cycle of therapy. The incidence of prolonged delays in treatment was decreased (Table 5).

The incidence of pneumonia was significantly decreased among treated patients compared with historical controls (8% vs 37%, p = 0.004). Comparison of courses in historical control patients during which pneumonia did or did not develop showed that the only significant factor was neutropenia. Pneumonia occurred in 16% of courses in which AGC was <0.5 x 109/L vs 8% of courses for which AGC was >0.5 x 109/L (p = 0.009) (38). The incidence of sepsis did not differ between treated and historical control patients in this relatively small trial. Filgrastim therapy was reported to be safe and well tolerated.

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