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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 837-845
Myelopoietin, an engineered chimeric IL-3 and G-CSF receptor
agonist, stimulates multilineage hematopoietic recovery in a nonhuman
primate model of radiation-induced myelosuppression
Thomas J. MacVittie,
Ann M. Farese,
Walter G. Smith,
Charles M. Baum,
Earl Burton, and
John P. McKearn
From the Greenebaum Cancer Center, University of Maryland,
Baltimore; and Searle R & D, Monsanto Company, St. Louis, MO.
Myelopoietins (MPOs) constitute a family of engineered, chimeric
molecules that bind and activate the IL-3 and G-CSF receptors on
hematopoietic cells. This study investigated the in vivo hematopoietic response of rhesus monkeys administered MPO after radiation-induced myelosuppression. Animals were total body irradiated (TBI) in 2 series,
with biologically equivalent doses consisting of either a 700 cGy dose
of Cobalt-60 (60Co)  -radiation or 600 cGy, 250 kVp
x-irradiation. First series: On day 1 after 700 cGy irradiation,
cohorts of animals were subcutaneously (SC) administered MPO at 200 µg/kg/d (n = 4), or 50 µg/kg/d (n = 2), twice daily, or
human serum albumin (HSA) (n = 10). Second series: The 600 cGy
x-irradiated cohorts of animals were administered either MPO at 200 µg/kg/d, in a daily schedule (n = 4) or 0.1% autologous serum
(AS) , daily, SC (n = 11) for 23 days. MPO regardless of
administration schedule (twice a day or every day) significantly reduced the mean durations of neutropenia (absolute neutrophil count
[ANC] < 500/µL) and thrombocytopenia (platelet < 20 000/µL) versus respective control-treated cohorts. Mean neutrophil and platelet
nadirs were significantly improved and time to recovery for neutrophils
(ANC to < 500/µL) and platelets (PLT < 20 000/µL) were
significantly enhanced in the MPO-treated cohorts versus controls. Red
cell recovery was further improved relative to control-treated cohorts
that received whole blood transfusions. Significant increases in bone
marrow-derived clonogenic activity was observed by day 14 after TBI in
MPO-treated cohorts versus respective time-matched controls. Thus, MPO,
administered daily was as effective as a twice daily schedule for
multilineage recovery in nonhuman primates after high-dose,
radiation-induced myelosuppression.
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