Highly Efficient Peripheral Blood Progenitor Cell Mobilization in Myeloma Patients by Single-Dose Application of 12 mg Pegylated G-CSF.

Autologous peripheral blood stem cell (PBSC) transplantation leads to significant prolongation of survival in patients with different malignancies. For PBSC mobilization a combination of myelosuppressive chemotherapy and granulocyte colony stimulating factor (G-CSF) are administered. The optimal application of G-CSF is twice daily. New G-CSF formulations with prolonged half-life carry the promise of reduced patient strain, increased compliance and via continuously high G-CSF serum levels possibly improved PBSC mobilization. We initiated a study with pegfilgrastim-supported mobilization chemotherapy in stage II and III myeloma patients. Patients received up-front treatment with three cycles of vincristin, doxorubicin, dexamethason (VAD) or thalidomide, doxorubicin, dexamethason (TAD).

The mobilization regime consisted of four days chemotherapy with cyclophosphamide 1g/m² day1, doxorubicin 15mg/m² day 1–4, dexamethason 40 mg d 1–4 p.o. (CAD) and a single administration of 12 mg pegfilgrastim subcutaneously on day five. 25 patients (median age 57, 12 female, 13 male) received pegfilgrastim and leukapheresis was started 6–17 days (mean 10 days) after treatment with a range of maximum CD34 cell count between 7,2 and 842 (mean: 119) CD34+ cells/μl peripheral blood. After leukapheresis 6.2 * 10e6 to 40.5 * 10e6 (mean 13.8 *10e6) CD34+ cells per kilogram body weight were collected. 11 patients achieved the target number of 7.5 * 10e6 CD34+ cells per kilogram body weight during a single apheresis, while 5 patients needed two, 7 patients needed three and 2 patients needed four apheresies on consecutive days. 3 patients required additional administration of filgrastim. 2 patients received 6 mg pegfilgrastim off study. Both achieved sufficient numbers of CD34+ cells (12.7 and 20.8 * 10e6 CD34+ per kg BW). There were only minimal adverse effects. Four patients reported of bone pain or nausea. Mobilization failures did not occur in this patient population. To date, 16 patients have been transplanted with a mean of 6,03* 10e6 CD34+ per kg BW (range 2,4 to 13,5). Reconstitution (reaching a leukocyte count of >1,0/nl) was reached within a mean of 13 days (range 11–21). On the basis of these first results we conclude that a single dose application of 12 mg pegfilgrastim after CAD treatment allows collection of more than 3 autografts in two or less apheresis session in the majority of myeloma patients. Reduction of apheresis sessions is a significant clinical cost-effectiveness end point in PBPC mobilization.