Single-Dose Pegfilgrastim after Chemotherapy Is Highly Effective in Enhancing the Mobilization of Autologous CD34+ Peripheral Blood Stem Cells in Patients with Lymphoid Malignancies and Solid Tumors.

The administration of myelosuppressive chemotherapy followed by daily injections of granulocyte-colony stimulating factor (G-CSF) is the common procedure to mobilize autologous CD34+ peripheral blood stem cells (PBPC). Pegfilgrastim (Neulasta^TM, 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. Whereas a single injection of pegfilgrastim (PEGFIL) has been shown to be equivalent to daily filgrastim in enhancing neutrophil recovery after chemotherapy, the experiences with PEGFIL in mobilization of PBPC are limited.

We report 40 pts (22 male, 18 female, median age 53 years) who had a PBPC mobilization treatment for Hodgkin′s lymphoma (n=3), non-Hodgkin′s lymphoma (n=13), multiple myeloma (n=16), acute lymphoblastic leukaemia (n=3) or solid tumors (n=5). The mobilization regimen consisted of disease specific chemotherapy and a single subcutaneous injection of 6 mg PEGFIL administered 48 hours after the end of cytotoxic treatment (day 0). CD34+ cells in the peripheral blood (PB-CD34) were measured if white blood cells (WBC) exceeded 1.0 Gpt/L after nadir. PBPC collections started at a PB-CD34 cell count >10/μl and were performed as large-volume apheresis (4x blood volume) using a Cobe Spectra (Gambro BCT Inc.). Additional conventional filgrastim (FIL) was given at a dose of 2x5μg/kg if PB-CD34 count was found to be <10/μl. Blood samples for pharmacokinetics were taken in 9 pts.

The median start of aphereses was on day +9 after the administration of PEGFIL and on day +15 after start of chemotherapy regimen, respectively. Median PB-CD34 peak was 74/μl (range 9–565/μl). The median PBPC yield was 7.6 x 10^6 CD34+ cells/kg (range 1.5–88.1). The target cell dose to be collected (≥ 2.5 x 10^6 CD34+ cells/kg) was achieved in 36 (90 %) pts, in 29 pts (72.5 %) ≥ 4.0 x 10^6 CD34+ cells/kg could be obtained with a single collection. Additional FIL administrations were necessary in 7 patients (17.5 %) for 2 to 6 days. All of them were heavily pretreated including a previous autologous transplant in two of these patients. PEGFIL was well tolerated except for moderate bone pain which occurred in all patients.

The mean values (± SD) for peak plasma concentration of PEGFIL (c_max), time to reach the maximum plasma level (t_max) and elimination half-life (t_1/2) were 154 (± 83) ng/ml, 56 (±21) hours and 23 (± 9) hours, respectively.

We conclude that a single dose of 6 mg PEGFIL after chemotherapy is safe and highly effective in enhancing the mobilization of CD34+ PBPC for stem cell collection. Further investigations are warranted, including comparison with non-pegylated G-CSFs and in combination with antiadhesive agents.