Daily G-CSF (filgrastim) and a Single Dose Of Pegylated G-CSF (pegfilgrastim) After Chemotherapy Result In Different Kinetics Of Circulating Hematopoetic Progenitors: Implication For Potential Stem Cell Harvesting

Several studies have shown that a single dose of pegylated G-CSF (pegfilgrastim, Neulasta®) administered after chemotherapy allows sufficient collection of hematopoietic progenitor cells (HPC) for autologous transplantation. Pegfilgrastim has not been approved for HPC mobilization, but the decision for stem cell harvesting may be made after pegG-CSF has already been given. In this case, particular kinetics of circulating HPC after pegG-CSF must be taken into account to guide stem cell harvesting. In an intra-individual analysis, we compared mobilization of HPC in 12 lymphoma patients undergoing two identical cycles of salvage chemotherapy (etoposide, ifosfamide, cisplatin, ± epirubicin, ± rituximab) within a clinical trial (ClinicalTrials.gov: NCT00306111). G-CSF (filgrastim, Neupogen® 5 ug/kg/d) was given daily after the 1st cycle starting at day 3, while a single dose of pegfilgrastim (Neulasta®, 6 mg) was administered after the 2nd cycle. Circulating HPC were analyzed by flow cytometry and colony assays. We found that neutrophil recovery was remarkably pronounced after pegG-CSF resulting in a significant higher white blood count at day 12 compared with filgrastim (WBC: 6.8 ± 1.9 G/l vs. 3.2 ± 0.8 G/l, mean ± SEM), but a similar WBC at day 14 and day 16. However, kinetics of circulating HPC were markedly different: A trend to higher numbers of CD34+ progenitors was observed after pegfilgrastim at day 12 compared to filgrastim, followed by a sharp drop at day 14: 25 ± 12 /μl (pegfilgrastim) vs. 69 ± 22 /μl (filgrastim). Particularly the number of more primitive CD34+CD38- progenitors was significantly reduced at day 14: 3.7 ± 3.0 /μl (pegfilgrastim) vs. 11.7 ± 6.3 /μl (filgrastim). Similar results were found for the more primitive CD34+CD133+ und CD34+CD90+ populations. The colony formation (cloning efficiency) of the HPC was not different. Also, coexpression of homing-related receptors (CXCR4, CD62L/L-selectin) was similar in both groups. We conclude that after chemotherapy and pegG-CSF, sufficient numbers of HPC are circulating which allows for HPC collection during the early recovery phase. However, the HPC count is rapidly dropping once the WBC has recovered, in line with the known elimination of pegGCSF by binding to neutrophils. Thus, when a stem cell harvest is scheduled after neutrophil recovery in these patients, daily addition of non-pegylated G-CSF should be considered.