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Pegylated megakaryocyte growth and development factor abrogates the lethal
thrombocytopenia associated with carboplatin and irradiation in mice
MM Hokom, D Lacey, OB Kinstler, E Choi, S Kaufman, J Faust, C Rowan, E Dwyer, JL Nichol and T Grasel
Amgen, Inc, Amgen Center, Thousand Oaks, CA 91320, USA.
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 thrombocytopenia that results
from the combination treatment of carboplatin and sublethal irradiation.
Mortality of this regimen is 94% and is associated with widespread internal
bleeding. The daily administration of pegylated recombinant human MGDF
(PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated
the depth and duration of thrombocytopenia. 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 normal platelets. PEG-rMGDF
administered in combination with murine granulocyte colony-stimulating
factor completely prevented mortality and further reduced leukopenia and
thrombocytopenia. These data support the concept that PEG-rMGDF may be
useful to treat iatrogenic thrombocytopenias.
Volume 86,
Issue 12,
pp. 4486-4492,
12/15/1995
Copyright © 1995 by The American Society of Hematology
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