Blood, Vol. 91 No. 5 (March 1), 1998:
pp. 1828-1829
CORRESPONDENCE
Schedule-Dependency of Granulocyte Colony-Stimulating Factor in
Peripheral Blood Progenitor Cell Mobilization in Breast Cancer Patients
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LETTER |
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 × 106
CD34+ 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 v
1.3 × 104/kg; P = .002 and 6.6 v
2.6 × 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 v
3.1 × 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.
Nicolaus Kröger
Wolfgang Zeller
Hassan T Hassan
William Krüger
Cornelius Löliger
Axel R Zander
Bone Marrow Transplantation
Center
University-Hospital Hamburg
Hamburg, Germany
| |
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