Feasibility and Efficacy of Peripheral Blood Progenitor Cell Mobilisation with Pegfilgrastim for Allogeneic Stem Cell Transplantation.
Authors: Kroschinsky Frank , Hoelig Kristina , Ordemann Rainer , Haack Astrid , Poppe-Thiede Kirsten , Blechschmidt Matthias , Rall Gabi , Bornhaeuser Martin , Schleyer Eberhard , Rutt Claudia , Ehninger Gerhard 
Published: April 2020

Abstract
Short-term administration of rhG-CSF is a safe and effective procedure for mobilization of allogeneic PBPC in healthy related and unrelated donors. Pegfilgrastim (Neulasta™, Amgen Inc., Thousand Oaks, USA) is a covalent conjugate of filgrastim and polyethylene glycol with an increased elimination half-life due to decreased serum clearance. In cancer patients a single injection of pegfilgrastim has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy.
However there are no data concerning the efficacy of pegfilgrastim in mobilization of allogeneic PBPC. We report on 20 allogeneic PBPC donors (11 related, 9 unrelated, 12 male, 8 female), who have undergone a mobilization treatment with pegfilgrastim. The median age was 43 (range 28–74) years. Donors received a single subcutaneous injection of 2 vials (12 mg) pegfilgrastim resulting in a median dose of 161 μg/kg body weight (range 126–187). Monitoring included complete blood cell counts, number of CD34+ cells in peripheral blood (PB-CD34), cytokine related side effects and in five donors filgrastim pharmacokinetics. PBPC were collected by large-volume leukaphereses (4x blood volume) using Cobe Spectra 7.0 (Gambro BCT Inc.).
Pegfilgrastim induced a rapid increase of WBC and ANC, which raised in median from 6.10 x 10^9/L at baseline to 34.41 x 10^9/L on day 2 and from 4.03 x 10^9/L to 28,05 x 10^9/L. Peak values of PB-CD34+ cells was found consistently on day 5 (median 76/μl, range 10–385). On day 6 the PB-CD34+ cell count was less than on day 5, and also less than on day 4 (day 6: median 38.5/μl, range 9–180; day 4: median 61.5/μl, range 4–135). In 19/20 donors the apheresis started on day 5. In a 74 years old family donor additional filgrastim at a dose of 10 μg/kg was administered on day 4 and 5 due to a PB-CD34+ cell count of 4/μl on day 4. The median apheresis yield was 8.23 x 10^6 CD34+ cells/kg donor weight (range 2.40–29.32), corresponding to a median of 9.5 x 10^6 CD34+ cells/kg recipient (range 3.22–39.71). The target cell dose (≥ 4.0 x 10^6 CD34+cells/kg recipient) was reached with one procedure in 15 (75 %) donors. Apheresis products contained in median 3.8 x 10^8 CD3+ T-cells. Mobilization and harvesting were well tolerated except for moderate bone pain which occurred in 19/20 donors. The mean values (± SD) for peak plasma concentration of pegfilgrastim (cmax), time to reach the maximum plasma level (tmax) and elimination half-life (t1/2) were 500 (± 417) ng/ml, 33 (±13) hours and 23 (± 9) hours, respectively. Among 14 recipients, who are evaluable for engraftment study at present, one graft failure occurred in a patient who received a haploidentical graft from her sibling donor.
Pegfilgrastim is able to mobilize a sufficient number of CD34+ PBPC for stem cell collection in allogeneic donors. Schedule for mobilization and apheresis is very similar to conventional, non-pegylated rhG-CSFs. However, the PB-CD34+ cells were found to be higher on day 4 than on day 6. Pegfilgrastim is well tolerated and side effects are similar to Filgrastim. The most important benefit for the donor is the simplified once-per-mobilization dosing. Further evaluation with respect to graft function and incidence of graft-versus-host-disease is ongoing.