Schedule-Dependency of Granulocyte Colony-Stimulating Factor in Peripheral Blood Progenitor Cell Mobilization in Breast Cancer Patients

To the Editor:

Glaspy et al1 reported on enhanced CD34⁺ cell yield when filgrastim is combined with stem cell factor (SCF) as to filgrastim alone (as 10 μg/kg daily injection) in breast cancer patients. A comparative enhanced CD34⁺ cell yield can be obtained by splitting the filgrastim dose into 2 × 5 μg/kg daily. We have evaluated the progenitor cell mobilization with granulocyte colony-stimulating factor (Filgrastim) alone in high-risk breast cancer patients in terms of progenitor cell dose and engraftment after high-dose chemotherapy using different schedules: 1 × 10 μg/kg daily or 2 × 5 μg/kg daily. Forty-nine women with high-risk breast cancer (n = 35, >10 positive lymphnodes; n = 9, locally advanced/inflammatory; n = 5, stage IV/no evidence of disease) and a median age of 43 years (range, 27 to 61) were enrolled. All women received an anthracycline-based induction chemotherapy (5-fluorouracil, Adriamycin, cyclophosphamide or epirubicin, cyclophosphamide [FAC or EC]). After complete hematological recovery the patients received 10 μg/kg G-CSF (Filgrastim; Amgen, Munich, Germany) daily subcutaneously; 27 patients received 10 μg/kg once daily whereas 22 patients received 5 μg/kg twice daily with a time interval of 12 hours. Leukapheresis was started on day 5 usually 2 to 3 hours after the last injection. G-CSF application was continued until completion of leukapheresis. High-dose chemotherapy was given after the fourth cycle induction therapy and consisted of cyclophosphamide (6,000 mg/m²), thiotepa (600 mg/m²), and mitoxantrone (40 mg/m²). Cytokine priming as well as collection of peripheral blood stem cells (PBSC) were well tolerated in both groups. Overall, 30% of the patients experienced mild myalgia or bone pain, and 15% required nonsteroidale analgetics. Overall, after a median of 2 leukapheresis (range, 1 to 3) a median number of 6.6 × 10⁶CD34⁺ cell kg (range, 1.0 to 57.3), of 7.4 × 10⁸ mononuclear cells (MNC) kg (range, 2.4 to 154.0) and of 3.7 × 10⁴ colony-forming unit–granulocyte macrophage (CFU-GM) kg (range, 0.2 to 47.9) were collected. The median leukocyte count before the first apheresis was 48.3/mL (range 11.3 to 85.6) and correlated with the CD34⁺ cell yield (range, 0.33;P = .01). The median leukocyte count before first apheresis was higher in the 2 × 5-μg group than in the 1 × 10-μg group (52.7/nL v 41.9/μL) resulting in a significantly higher CD34⁺ cell count in the first apheresis (5.8 v 1.9 × 10⁶/kg; P = .003). Additionally the median CFU-GM and the median MNC were significantly higher in the 2 × 5 μg/kg than in the 1 × 10 μg/kg group (6.5 v1.3 × 10⁴/kg; P = .002 and 6.6 v2.6 × 10⁸/kg; P < .001). Also, the median erythroid burst-forming unit (BFU-E) was higher in the 2 × 5 μg than in the 1 × 10 μg group (9.2 v3.1 × 10⁴/kg; P = .01). The higher CD34⁺ cell yield of the 2 × 5-μg/kg group resulted in less aphereses procedures than in the 1 × 10-μg group (mean, 1.8 v 2.3;P = .01).

All patients engrafted with leukocyte counts greater than 1.0/nL after a median of 10 days (range 8 to 15) and platelet counts greater than 50/nL after a median of 12 days (range, 5 to 41). There was no difference in leukocyte and platelet engraftment between the two different schedules (10 v 10 days, and 12 v 13 days).

Another possibility to enhance CD34⁺ cell yield can be also obtained by increasing the filgrastim dose in lymphoma patients.2 In breast cancer patients a dose-response effect of G-CSF has also been reported.3-5 But similiar as the addition of SCF, increasing the dose of filgrastim results in slight increase of toxicity and high increase of costs. By splitting the dose of 10 μg/kg daily to 2 × 5 μg/kg daily a higher yield of CD34⁺ cells and CFCs can be obtained without increasing costs and toxicity.