The role of pegfilgrastim in mobilization of hematopoietic stem cells.

摘要

Granulocyte colony-stimulating factors (G-CSF) are established prerequisites for the mobilization of peripheral blood stem cells (PBSC). Pegylated filgrastim (pegfilgrastim) has a substantially increased elimination half-life due to decreased serum clearance. A single-dose of pegfilgrastim is equivalent in enhancing neutrophil recovery after chemotherapy compared to daily filgrastim administrations. Several clinical trials also investigated chemotherapy plus single-dose pegfilgrastim in the mobilization of autologous PBSC in patients with lymphoma or myeloma. The results indicated similar efficacy compared to unconjugated G-CSF in terms of blood CD34+ cell count, stem cell yields as well as engraftment of after reinfusion. However, the number of patients in these trials were limited and there were non-randomized controls only. Furthermore, the mobilization of 12 mg pegfilgrastim was not superior over the 6 mg dose, and in one trial insufficient results were observed in heavily pretreated patients. In allogeneic stem cell donors a single-dose of 12 mg pegfilgrastim has been shown to induce a sufficient increase of blood CD34+ cells with a similar kinetics as known from conventional G-CSF. Adequate numbers of PBSC for transplantation could be harvested mostly by a single apheresis. Bone pain and headaches appeared to be more severe and about 90% of donors required analgetics. Additional concerns are due to spleen enlargement and hyperleukocytosis. Promising insights were reported from preclinical studies which revealed a modulating impact on both graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after transplantation of pegfilgrastim mobilized PBSC. Further trials are needed which carefully evaluate the issues of donor safety, but also the impact on graft composition and recipients' outcome.