Fludarabine and granulocyte colony-stimulating factor (G-CSF) in patients with chronic lymphocytic leukemia

Abstract

The study was designed to determine whether administration of granulocyte colony-stimulating factor (G-CSF) following fludarabine would reduce the incidences of myelosuppression and infections. Twenty-five previously treated patients with Rai stage III–IV chronic lymphocytic leukemia (CLL) received fludarabine 30 mg/m² daily for 5 days each month. G-CSF was given at 5 μg/kg subcutaneously starting 1 day after chemotherapy (day 6) and continued until the next course unless the granulocyte count was ⩾10 000/μl. The incidences of myelosuppression and infection were compared with those seen in an historical control population of 145 previously treated patients with Rai stage III–IV CLL who were given the same schedule of fludarabine without growth factor. There was a significant decrease in myelosuppression; patients receiving G-CSF developed neutropenia at a neutrophil count <1000/μl or 500/μl in 45% and 15% of courses vs 79% (P = 0.002) and 63% (P < 0.001) of historical controls. twenty percent of g-csf-treated patients had therapy delayed by >35 days per course, vs 50% of historical controls (P = 0.005). The incidence of pneumonia was 8% with G-CSF and 37% without in historical controls. Other infection rates (sepsis, fever of undetermined origin, minor infections) were similar. This decrease in pneumonia was noted even in high-risk groups such as patients older than 60 years and patients with hypogammaglobulinemia. The use of G-CSF following fludarabine in high-risk patients with CLL resulted in a significant decrease in myelosuppression and pneumonia. Larger trials to verify these results and to compare costs are indicated.