Dahl E, Burroughs J, DeFor T, Verfaillie C, Weisdorf D
Blood and Marrow Transplant Program and the Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
Bone Marrow Transplant. 2003 Sep;32(6):575-80. doi: 10.1038/sj.bmt.1704237.
The progenitor content of autologous peripheral blood progenitor and stem cell collections is a major determinant of prompt hematopoietic recovery following autologous stem cell transplantation. We analyzed unstimulated bone marrow (BM) and peripheral blood (PB) apheresis products in comparison to those collected following G-CSF or GM-CSF stimulation. We quantitated their committed (CFU-GM) and primitive (long-term culture-initiating cells, LTC-IC) progenitors in relation to hematologic recovery in 63 patients undergoing autografting for lymphoid malignancies. G-CSF, but not GM-CSF, substantially enriched the committed progenitor content (2.5-3.6-fold) of both PB and BM grafts. G-CSF also enriched the LTC-IC content of BM and PB compared to control grafts. GM-CSF augmented (11.5-fold) the LTC-IC content of stimulated BM, but not GM-CSF-mobilized PB. Neutrophil recovery was substantially quicker in recipients of BM or PB mobilized with G-CSF or GM-CSF. In contrast, red cell and platelet recovery was accelerated in recipients of GM-CSF-stimulated BM (but not PB) and G-CSF-stimulated PB (but not BM). No direct correlation between progenitor dose and hematopoietic recovery for neutrophils, platelets or red cells was observed. Cytokine stimulation can augment the committed and more primitive multilineage progenitor content of BM and PB grafts, to a differing extent. The uncertain relationship with multilineage myeloid recovery emphasizes the limitations in using clonogenic progenitor analyses to assess the adequacy of an autologous graft prior to transplantation.
自体外周血祖细胞和干细胞采集物中的祖细胞含量是自体干细胞移植后造血迅速恢复的主要决定因素。我们分析了未刺激的骨髓(BM)和外周血(PB)单采产物,并与粒细胞集落刺激因子(G-CSF)或粒细胞-巨噬细胞集落刺激因子(GM-CSF)刺激后采集的产物进行比较。我们对63例因淋巴系统恶性肿瘤接受自体移植的患者,定量分析了其定向祖细胞(粒-巨噬细胞集落形成单位,CFU-GM)和原始祖细胞(长期培养起始细胞,LTC-IC)与血液学恢复的关系。G-CSF而非GM-CSF显著增加了PB和BM移植物中定向祖细胞的含量(2.5至3.6倍)。与对照移植物相比,G-CSF还增加了BM和PB中LTC-IC的含量。GM-CSF增加了(11.5倍)受刺激BM中LTC-IC的含量,但未增加GM-CSF动员的PB中LTC-IC的含量。接受G-CSF或GM-CSF动员的BM或PB的受者中性粒细胞恢复明显更快。相比之下,接受GM-CSF刺激的BM(而非PB)和G-CSF刺激的PB(而非BM)的受者红细胞和血小板恢复加快。未观察到祖细胞剂量与中性粒细胞、血小板或红细胞造血恢复之间的直接相关性。细胞因子刺激可不同程度地增加BM和PB移植物中定向和更原始的多谱系祖细胞含量。与多谱系髓系恢复的不确定关系强调了在移植前使用克隆形成祖细胞分析评估自体移植物充足性的局限性。