Molineux G, Hartley C, McElroy P, McCrea C, McNiece I K
Department of Developmental Hematopoiesis, Amgen Inc, Thousand Oaks, CA, 91320, USA.
Blood. 1996 Jul 1;88(1):366-76.
We have investigated the potential of PEGylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), a molecule related to thrombopoietin (mpl ligand or TPO) in minimizing the thrombocytopenia associated with hematopoietic ablation and peripheral blood progenitor cell (PBPC) transplant. Irradiated mice that received PBPC mobilized by PEG-rHuMGDF or granulocyte colony-stimulating factor (G-CSF) had a reduced number of thrombocytopenic days with platelets below 100 x 10(6) per mL of blood. Recipients of unmobilized PBPC had a 9 day thrombocytopenic phase which was shortened to 7 days if they were given granulocyte-macrophage colony-stimulating factor (GM-CSF)-mobilized PBPC. This was further reduced to 2 or 3 days of thrombocytopenia in recipients of G-CSF- or PEG-MGDF-mobilized PBPC. Despite our observation that PEG-rHuMGDF is a relatively modest stimulator of the mobilization of myeloid progenitors to the blood, MGDF-mobilized PBPC do effect accelerated recovery of platelets after transplantation. However, the most effective use of PEG-rHuMGDF is when it is given during the recovery phase after PBPC transplantation to hematopoietically ablated mice. Posttransplant treatment with PEG-rHuMGDF reduces thrombocytopenia to a single day or less, in recipients of most types of PBPC. Mice that were treated during the first 2 weeks after PBPC transplant with PEG-rHuMGDF had 1 thrombocytopenic day compared to 9 days in carrier-treated recipients of unmobilized PBPC and 2 to 3 days in carrier-treated recipients of the optimally mobilized PBPC from G-CSF or G-CSF/PEG-rHuMGDF treated donors. In groups where PEG-rHuMGDF was included in the mobilization protocol and used to treat recipients as well thrombocytopenia was effectively eliminated. These data show that PEG-rHuMGDF is a highly effective agent in eliminating the thrombocytopenia associated with PBPC transplantation.
我们研究了聚乙二醇化重组人巨核细胞生长和发育因子（PEG-rHuMGDF）的潜力，该分子与血小板生成素（mpl配体或TPO）相关，可最大程度减少与造血干细胞清除和外周血祖细胞（PBPC）移植相关的血小板减少症。接受PEG-rHuMGDF或粒细胞集落刺激因子（G-CSF）动员的PBPC的受辐照小鼠，血小板计数低于每毫升血液100×10⁶的血小板减少天数减少。未动员的PBPC受者有9天的血小板减少期，如果给予粒细胞-巨噬细胞集落刺激因子（GM-CSF）动员的PBPC，则缩短至7天。在接受G-CSF或PEG-MGDF动员的PBPC的受者中，血小板减少症进一步减少至2或3天。尽管我们观察到PEG-rHuMGDF对骨髓祖细胞动员到血液中的刺激作用相对较小，但MGDF动员的PBPC确实能在移植后加速血小板的恢复。然而，PEG-rHuMGDF最有效的使用方式是在PBPC移植后给予造血干细胞清除的小鼠恢复期。PEG-rHuMGDF的移植后治疗可将大多数类型PBPC受者的血小板减少症减少至1天或更短时间。在PBPC移植后前2周用PEG-rHuMGDF治疗的小鼠有1天血小板减少期，而未动员的PBPC接受载体治疗的受者有9天，接受G-CSF或G-CSF/PEG-rHuMGDF治疗供体的最佳动员的PBPC接受载体治疗的受者有2至3天。在动员方案中包含PEG-rHuMGDF并用于治疗受者的组中，血小板减少症也得到了有效消除。这些数据表明，PEG-rHuMGDF是消除与PBPC移植相关的血小板减少症的高效药物。
