Factors influencing G-CSF-mediated mobilization of hematopoietic progenitor cells during steady-state hematopoiesis in patients with malignant lymphoma and multiple myeloma

Abstract

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.

Improving stem cell mobilization strategies: future directions

“…Positive results historically reported for high-dose G-CSF remobilization regimens 83,90 have not been notably strengthened or refuted by recent research. 23,93 Gazitt et al 83 reported that the administration of G-CSF 32 mg/kg s.c. daily for 4 days before apheresis and continuing until the last day of apheresis resulted in successful remobilization in 88% of 18 patients whose first mobilization attempt was unsuccessful; most of these patients had NHL.…”

Blood stem cell collections in multiple myeloma: definition of a scoring system

“…Recent observations support the use of G-CSF alone used at higher dosage, particularly in heavily treated cancer patients. [8][9][10][11] Since the number of CD34 + stem cells has been shown to be the most important factor for a rapid hematological reconstitution, many studies have tried to establish their optimal dose. A number ranging between 2.0 and 5.0 × 10 6 /kg seems adequate for a good engraftment, [12][13][14] with a threshold of Ͼ1.0 × 10 6 in patients without extensive prior chemoradiotherapy and у2 × 10 6 in all others.…”

Pegfilgrastim for PBSC mobilization and autologous haematopoietic SCT

“…It is agreed on that doses in the range of 5-15 mg/kg body weight produce similar results and that the dose of G-CSF administered after cytotoxic chemotherapy plays a far less important role in the extent of stem cell mobilization compared with the administration of G-CSF alone during steady state conditions. 10,11 Other factors are more relevant to the extent of stem cell mobilization after chemotherapy, particularly the myelotoxicity of the chemotherapy, the extent of earlier chemotherapy and/or radiotherapy and the age of the patient. [11][12][13] As sequential high-dose therapies provide a therapeutic advantage in some disorders, such as multiple myeloma, it is of particular importance that sufficient quantities of blood stem cells are obtained during one mobilization cycle.…”

“…10,11 Other factors are more relevant to the extent of stem cell mobilization after chemotherapy, particularly the myelotoxicity of the chemotherapy, the extent of earlier chemotherapy and/or radiotherapy and the age of the patient. [11][12][13] As sequential high-dose therapies provide a therapeutic advantage in some disorders, such as multiple myeloma, it is of particular importance that sufficient quantities of blood stem cells are obtained during one mobilization cycle. 14 Cytotoxic blood stem cell mobilization with pegfilgrastim in patients with haematological malignancies After it had been clearly shown that a single dose of a pegylated G-CSF, after conventional chemotherapy, with prolonged half-life (pegfilgrastim) was equivalent to the daily administration of G-CSF, it seemed likely that pegfilgrastim could also be used for the mobilization of autologous haematopoietic progenitor cells.…”

“…With this method, the progenitor cell peak is reached between days 5 and 6. 11 The extent of mobilization is determined by the age of the patient, the diagnosis, the earlier cytotoxic therapy, the dose of G-CSF and the sequence of G-CSF administration. 32 Kroger et al, 33 for example, were able to show that mobilization was more effective if the total dose of G-CSF was divided into two equal fractions and given in the morning and in the evening rather than as a single dose once daily.…”