Thrombopoietin Promotes Mobilization of Peripheral Blood Progenitor Cells

Several pilot studies evaluated the activity of various doses and schedules of rHuTPO or PEG-rHuMGDF in combination with rHuG-CSF and chemotherapy as part of a mobilization regimen for stem cell transplantation (94,107,117-120). In contrast to the peak progenitor cell numbers on d 5-7 usually obtained with rHuG-CSF alone, a peak on d 12-15 was produced by the combination of PEG-rHuMGDF and rHuGCSF. PEG-rHuMGDF produced a 250-fold increase in the number of circulating Meg-CFC, a 190-fold increase in GM-CFC, a 65-fold increase in erythroid blast-forming cells (E-BFC), and a 24-fold increase in CD34+ cells compared with patients receiving only chemotherapy and rHuG-CSF (107). However, since a full pharmacodynamic response profile to PEG-rHuMGDF was not done in this study, the exact day of peak stem cell mobilization was not determined. In a separate study, the addition of rHuTPO to rHuG-CSF for chemotherapy mobilization regimens substantially increased CD34+ yields. Treatment with rHuTPO in various doses and schedules reduced the number of aphereses needed to reach a target graft (i.e., CD34+ > 5 x 106/kg) and, compared with placebo treatment, increased the percentage of patients reaching a target graft (from 46% in the placebo group to 79% in the rHuTPO group), as well as the percentage of patients reaching the minimum target graft (i.e., CD34+ > 2 x 106/kg; from 75% in the placebo group to 94% in the rHuTPO group).

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