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Synergistic effects of thrombopoietin and granulocyte colony- stimulating
factor on neutrophil recovery in myelosuppressed mice
A Grossmann, J Lenox, TA Deisher, HP Ren, JM Humes, K Kaushansky and KH Sprugel
ZymoGenetics Inc, Seattle, WA 98102-3702, USA.
Severe suppression of the hematopoietic system is a major factor in
limiting chemotherapy dose escalation. To determine whether a combination
of human recombinant granulocyte colony-stimulating factor (G-CSF) and
thrombopoietin (TPO) would alter recovery of platelets, red blood cells
(RBCs), or neutrophils after myeloablative therapy, myelosuppressed mice
were treated with sc injections of TPO (90 micrograms/kg), G-CSF (250
micrograms/kg). TPO plus G-CSF or vehicle and complete blood counts were
measured. Marrow and spleen cells were obtained at various times and
assayed for erythroid, myeloid, and megakaryocytic progenitors. The
prolonged neutropenia in vehicle controls (14 days) was significantly
shortened in mice treated with G- CSF or TPO for 14 days. The combination
of TPO plus G-CSF further reduced the duration of neutropenia. TPO and TPO
plus G-CSF treatments also significantly shortened thrombocytopenia
compared to vehicle. Recovery of RBCs was also enhanced in mice treated
with either G-CSF or TPO, or the combination. Furthermore, treatment with
G-CSF and/or TPO hastened myeloid, erythroid, and megakaryocyte progenitor
recovery compared to vehicle controls. These results show that the
combination of TPO plus G-CSF acts synergistically to accelerate neutrophil
recovery in myelosuppressed mice and does not compromise the platelet or
RBC response to TPO therapy.
Volume 88,
Issue 9,
pp. 3363-3370,
11/01/1996
Copyright © 1996 by The American Society of Hematology

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