Schriber J R, Negrin R S, Chao N J, Long G D, Horning S J, Blume K G
Department of Medicine, Stanford University Hospital, CA 94305.
Leukemia. 1993 Oct;7(10):1491-5.
Cloned colony-stimulating factors have been shown to accelerate myeloid recovery following autologous bone marrow transplantation. Studies with granulocyte-macrophage colony-stimulating factor (GM-CSF) have demonstrated efficacy in accelerating neutrophil recovery in patients rescued from myeloablative therapy. In our previous study, however, the subset of patients who received monoclonal antibody and complement purged bone marrow grafts followed by GM-CSF recovered neutrophil counts at the same rate as placebo-treated patients. We have now performed a phase II trial to assess whether granulocyte colony-stimulating factor (G-CSF) results in accelerated engraftment in this group of patients. Twenty-three consecutive patients with recurrent non-Hodgkin's lymphoma received G-CSF (10.5 +/- 1.2 micrograms/kg per day) following myeloablative therapy consisting of etoposide (60 mg/kg), cyclophosphamide (100 mg/kg), and either carmustine (15 mg/kg) or fractionated total body irradiation (1200 cGy). All patients received bone marrow grafts which had been purged with a panel of monoclonal antibodies directed against either B or T cell determinants plus complement. Peripheral blood mononuclear cells (PBMC) were not administered to any of the patients in this study. Twenty-one patients engrafted at a median absolute neutrophil count (ANC) greater than 500/microliters at day 12 and ANC greater than 1000/microliters at day 14. The time to myeloid engraftment was significantly shortened compared to our previous experience with either GM-CSF or placebo following identical preparatory regimens (p < 0.01). G-CSF is capable of accelerating myeloid engraftment in patients receiving monoclonal antibody purged bone marrow grafts following myeloablative therapy when compared to historical control groups treated with placebo or GM-CSF.
克隆的集落刺激因子已被证明可加速自体骨髓移植后的髓系恢复。粒细胞-巨噬细胞集落刺激因子(GM-CSF)的研究表明,其在加速接受清髓性治疗患者的中性粒细胞恢复方面具有疗效。然而,在我们之前的研究中,接受单克隆抗体和补体清除的骨髓移植并随后使用GM-CSF的患者亚组,其中性粒细胞计数恢复速度与接受安慰剂治疗的患者相同。我们现在进行了一项II期试验,以评估粒细胞集落刺激因子(G-CSF)是否能使该组患者的植入加速。23例复发性非霍奇金淋巴瘤患者在接受由依托泊苷(60mg/kg)、环磷酰胺(100mg/kg)以及卡莫司汀(15mg/kg)或分次全身照射(1200cGy)组成的清髓性治疗后,接受G-CSF(每天10.5±1.2μg/kg)。所有患者均接受了用一组针对B或T细胞决定簇的单克隆抗体加补体清除的骨髓移植。本研究中没有任何患者接受外周血单个核细胞(PBMC)。21例患者在第12天的中位绝对中性粒细胞计数(ANC)大于500/μl,在第14天ANC大于1000/μl时实现植入。与我们之前在相同预处理方案后使用GM-CSF或安慰剂的经验相比,髓系植入时间显著缩短(p<0.01)。与用安慰剂或GM-CSF治疗的历史对照组相比,G-CSF能够加速接受单克隆抗体清除的骨髓移植的患者在清髓性治疗后的髓系植入。