Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma.
We retrospectively analyzed factors influencing PBPC mobilization during steady-state hematopoiesis in 52 patients with malignant lymphoma (n=35) or multiple myeloma (n=17) who received 77 cycles of G-CSF (12.5-50 microg G-CSF/kg/day). For 15 of these patients, the first mobilization cycle (12.5 microg G-CSF/kg/day) was followed by a second course with an increased dose of G-CSF (25 or 50 microg/kg/day). Leukapheresis was started on day 4, about 2 h after s.c. G-CSF administration, and repeated on 2-5 consecutive days. CD34+ cells were determined by flow cytometry in each apheresis product and in the peripheral blood prior to G-CSF administration, beginning on day 4. Colony assays were performed on cryopreserved samples prior to autografting. In the 15 patients receiving two mobilization cycles the higher G-CSF dose was associated with higher levels of CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful (>2x10(6) CD34+ cells/kg) collections (p=0.058). Patients with limited previous cytotoxic therapy (n=19, up to six cycles of a standard regimen such as CHOP and/or less than 20% marrow irradiation) who received a daily dose of 12.5 microg G-CSF/kg had higher levels of circulating CD34+ cells, a higher mean yield of CD34+ cells per apheresis (p<0.05), and a higher percentage of successful collections (p<0.05) compared with patients previously treated with more intensive radiochemotherapy (n=15). Ten of 20 patients (50%) who failed during the first cycle were successful during subsequent cycles with escalated doses of G-CSF. Trough levels of circulating CD34+ cells on day 4 were predictive for success or failure to achieve >2x10(6) CD34+ cells/kg, especially in heavily pretreated patients. In conclusion, a daily dose of 12.5 microg G-CSF/kg seems sufficient to mobilize PBPC during steady-state hematopoiesis in the majority of patients who have received limited previous radiochemotherapy. Higher doses of G-CSF, up to 50 microg/kg/day, mobilize more PBPC and should be considered for patients previously treated with intensive radiochemotherapy or those failing to mobilize sufficient numbers of CD34+ cells with lower doses of G-CSF.
Kobbe
G
G
Department of Hematology. Oncology and Clinical Immunology, Heinrich Heine University Düsseldorf, Moorenstr. 5, D-40225 Düsseldorf, Germany.
Söhngen
D
D
Bauser
U
U
Schneider
P
P
Germing
U
U
Thiele
K P
KP
Rieth
C
C
Hünerlitürkoglu
A
A
Fischer
J
J
Frick
M
M
Wernet
P
P
Aul
C
C
Heyll
A
A
D000328:Adult; D018952:Antigens, CD34 / Q000032:analysis; D003603:Cytotoxins / Q000627:therapeutic use; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000276:immunology; D006801:Humans; D008223:Lymphoma / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood*; D011237:Predictive Value of Tests; D013997:Time Factors
D018952:Antigens, CD34; D003603:Cytotoxins; D016179:Granulocyte Colony-Stimulating Factor