Combined administration of recombinant human megakaryocyte growth and development factor and granulocyte colony-stimulating factor enhances multilineage hematopoietic reconstitution in nonhuman primates after radiation-induced marrow aplasia

This study compared the therapeutic potential of recombinant, native versus pegylated megakaryocyte growth and development factor (rMGDF and PEG-rMGDF, respectively), as well as that of the combined administration of PEG-rMGDF and r-methionyl human granulocyte colony-stimulating factor (r-metHuG-CSF) on hematopoietic reconstitution after 700 cGy, Co-60 gamma, total body irradiation in nonhuman primates. After total body irradiation, animals received either rMGDF, PEG-rMQF, r-metHuG-CSF, PEG-rMGDF and r-metHuG-CSF, or HSA, Cytokines in all MGDF protocols were administered daily for 18 d, HSA and r-metHuG-CSF alone were administered for 21-23 d. Either rMGDF, PEG-rMGDF, or PEG-rMGDF and r-metHuG-CSF administration significantly diminished the thrombocytopenic duration (platelet count [PLT] < 20,000/mu l) to 0.25, 0, and 0.5 d, respectively, and the severity of the PLT nadir (28,000, 43,000, and 30,000/mu 1, respectively) as compared with the controls (12.2 d duration, nadir 4,000/mu l), and elicited an earlier PLT recovery, Neutrophil regeneration was augmented in all cytokine protocols and combined PEG-rMGDF and r-metHuG-CSF further decreased the duration of neutropenia compared with r-metHuG-CSF alone. These data demonstrated that the administration of PEG-rMGDF significantly induced bone marrow regeneration versus rMGDF, and when combined with r-metHuG-CSF significantly enhanced multilineage hematopoietic recovery with no evidence of lineage competition.