PEGYLATED MEGAKARYOCYTE GROWTH AND DEVELOPMENT FACTOR ABROGATES THE LETHAL THROMBOCYTOPENIA ASSOCIATED WITH CARBOPLATIN AND IRRADIATION IN MICE

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias . This report describes a murine model of life-threatening thrombocyto penia that results from the combination treatment of carboplatin and s ublethal irradiation. Mortality of this regimen is 94% and is associat ed with widespread internal bleeding. The daily administration of pegy lated recombinant human MGDF (PEG-rMGDF) significantly reduced mortali ty (to <15%) and ameliorated the depth and duration of thrombocytopeni a. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from n ormal platelets. PEG-rMGDF administered in combination with murine gra nulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support th e concept that PEG-rMGDF may be useful to treat iatrogenic thrombocyto penias. (C) 1995 by The American Society of Hematology.