Kroschinsky Frank, Hölig Kristina, Ehninger Gerhard
Medical Department I, Dresden University Hospital, Fetscherstrasse 74, Dresden, Germany.
Transfus Apher Sci. 2008 Jun;38(3):237-44. doi: 10.1016/j.transci.2008.04.007. Epub 2008 May 19.
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.
粒细胞集落刺激因子（G-CSF）是动员外周血干细胞（PBSC）的既定前提条件。聚乙二醇化非格司亭（培非格司亭）由于血清清除率降低，其消除半衰期大幅延长。与每日注射非格司亭相比，单剂量培非格司亭在化疗后促进中性粒细胞恢复方面效果相当。多项临床试验还研究了化疗联合单剂量培非格司亭用于淋巴瘤或骨髓瘤患者自体PBSC的动员。结果表明，在血液CD34+细胞计数、干细胞产量以及再输注后的植入方面，与未结合的G-CSF相比疗效相似。然而，这些试验中的患者数量有限，且仅有非随机对照。此外，12mg培非格司亭的动员效果并不优于6mg剂量，并且在一项试验中，预处理严重的患者观察到的结果并不充分。在异基因干细胞供者中，已证明单剂量12mg培非格司亭可诱导血液CD34+细胞充分增加，其动力学与传统G-CSF相似。大多数情况下，通过单次采集就可以收获足够数量用于移植的PBSC。骨痛和头痛似乎更为严重，约90%的供者需要使用镇痛药。其他问题还包括脾肿大和白细胞增多。临床前研究报告了一些有前景的见解，这些研究揭示了培非格司亭动员的PBSC移植后对移植物抗宿主病（GVHD）和移植物抗白血病（GVL）效应均有调节作用。需要进一步开展试验，仔细评估供者安全性问题，以及对移植物组成和受者结局的影响。
