MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR STIMULATES ENHANCED PLATELET RECOVERY IN MICE AFTER BONE-MARROW TRANSPLANTATION

Megakaryocyte growth and development factor (MGDF) is a recently chara cterized ligand for the cell surface receptor mpl, We have evaluated t he effects of polyethylene glycollated recombinant human MGDF (PEG-rHu MGDF) on recovery of hematopoietic cells in mice following bone marrow transplantation (BMT) to support lethal irradiation. Mice treated wit h PEG-rHuMGDF (50 mu g/kg/d) had accelerated recovery of platelet numb ers compared with BMT mice treated with carrier or recombinant human g ranulocyte colony-stimulating factor (rHuG-CSF, 72 or 200 mu g/kg/d). In contrast, PEG-rHuMGDF had no effect on white blood cell (WBC) or re d blood cell (RBC) recovery, As previously reported, animals treated w ith rHuG-CSF had an enhanced recovery of WBC but not platelet or RBC l evels, Interestingly, BMT recipient mice treated with the combination of PEG-rHuMGDF and rHuG-CSF showed simultaneous enhanced recovery of b oth leukocytes and platelets, PEGylated rHuMGDF was found to be consid erably more potent than non-PEGylated rHuMGDF in this setting, PEG-rHu MGDF is an effective growth factor for enhancing platelet recovery in mice following BMT either alone or in combination with rHuG-CSF, It wi ll be of interest to evaluate in a clinical setting the ratios of PEG- rHuMGDF and rHuG-CSF for simultaneous administration of these factors and accelerated recovery of both leukocytes and platelets. (C) 1996 by The American Society of Hematology.