Mobilisation of Autologous Stem Cells Using a Single Fixed Dose Injection of Pegfilgrastim; Feasibility in Extensively Pre-Treated Lymphoma and Myeloma Patients.
Authors: Ypma Paula F. , Muradin Arif A. , Wijermans P.W. 
Published: October 2019

Abstract
In patients with multiple myeloma and refractory or relapsed lymphoma consolidation high-dose chemotherapy combined with stem cell rescue is an established therapy in chemosensitive disease. A commonly used approach to mobilise CD34+ haematopoietic stem cells is the administration of granulocyte colony-stimulating factor following a course of chemotherapy. Pegylation of filgrastim decreases renal clearance of the molecule. Pegfilgrastim is subject to a distinct method of clearance compared to filgrastim. The clearance therefore depends almost solely on a neutrophil receptor mediated process. This means clearance is self-regulated and increases when the number of neutrophils with G-CSF receptors augments in the blood. In earlier series of patients, pegfilgrastim showed to be effective in mobilising blood progenitor cells in single fixed doses of 6 mg. as well as 12 mg. The optimal dose and scheduling of the injection and apheresis is not completely established in various patients groups with diverse extents of chemotherapeutic pre-treatment. In this study we compared the mobilisation kinetics of patients with different haematological malignancies using either filgrastim or one injection of pegfilgrastim in two different doses. 58 patients with various indications for autologous stem cell transplantation were studied. The transplantation indications were multiple myeloma, NHL and Hodgkin’s lymphoma. Patients received a single dose of either 6 mgs or 12 mgs of pegfilgrastim; a third group of patients was treated with filgrastim daily. Filgrastim administration was stopped as soon as sufficient numbers of stem cells were harvested. Harvesting in both groups started as soon as an absolute CD 34+ count of >1 × 107 per litre was reached. The required number of stem cells was 3 × 106/kg bodyweight (6 × 106/kg in multiple myeloma patients). Mobilisation kinetics and apheresis results were compared in the three groups. The one-way analysis of variance (ANOVA) was used to compare the data.
26 Patients received a single dose of 6 mgs pegfilgrastim and 10 patients received a dose of 12 mgs of pegfilgrastim. 22 Patients, matched for disease type and pre-treatment regimens, age and gender received filgrastim daily. The filgrastim was administered in an average total dose of 4,2 mgs. (7,7 m gr./kg/day). Table 1 shows results of the apheresis. Of 26 patients who received pegfilgrastim 6 mgs, 5 patients showed a failure mobilising stemcells (21%). In 2 of those 5 patients harvesting succeeded eventually after additional stimulation with filgrastim and another 2 patients were mobilised in a later stage after additional chemopriming and filgrastim in high dosage. One of the patients receiving 12 mgs. of pegfilgrastim also needed additional filgrastim administration. None of the filgrastim mobilisation procedures failed. The results indicate that a single dose pegfilgrastim of 6 mgs is not capable of mobilising sufficient peripheral blood stem cells in all patients. In this study, both doses of pegfilgrastim showed a reduced CD34 cells harvest and less efficient apheresis procedures.
Table 1: Results Apheresis pegfilgrastim pegfilgrastim filgrastim 6 mg (n=26) 12 mg (n=10) (n=22) * p<0,05 day 1st apheresis, mean (SD) * 12.2 (1.4) 12.1 (0.9) 13.5 (2.4) max. blood CD34+ count (×107/L), mean (SD) 8.6 (7,7) 7.9 (6,6) 11.6 (10) number CD34+ cells (×106/kg), mean (SD) 8.2 (4.6) 8 (2,5) 11 (6,2) number CD34+ cells (×106/kg)per litre proc. volume, mean (SD) * 440 (290) 461 (350) 797 (650) failure apheresis 5 1 0