Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia

Hiromichi Akahori; Kazunori Shibuya; Masako Obuchi; Yoshito Nishizawa; Akio Tsuji; Koji Kabaya; Masaru Kusaka; Hideya Ohashi; Haruhiko Tsumura; Takashi Kato; Hiroshi Miyazaki

doi:10.1046/j.1365-2141.1996.d01-1842.x

Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia

Hiromichi Akahori^*, Kazunori Shibuya, Masako Obuchi, Yoshito Nishizawa, Akio Tsuji, Koji Kabaya, Masaru Kusaka, Hideya Ohashi, Haruhiko Tsumura, Takashi Kato, Hiroshi Miyazaki

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

50 Citations (Scopus)

Abstract

We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey's serum once each day from day 1 to day 2.8. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTP0-treated animals exhibited no significant-changes in several serum parameters, C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

Original language	English
Pages (from-to)	722-728
Number of pages	7
Journal	British Journal of Haematology
Volume	94
Issue number	4
DOIs	https://doi.org/10.1046/j.1365-2141.1996.d01-1842.x
Publication status	Published - 1996 Jan 1
Externally published	Yes

Keywords

Chemotherapy
Neutropenia
Primates
Thrombocytopenia
Thrombopoietin

ASJC Scopus subject areas

Hematology

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10.1046/j.1365-2141.1996.d01-1842.x

Cite this

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title = "Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia",

abstract = "We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey's serum once each day from day 1 to day 2.8. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTP0-treated animals exhibited no significant-changes in several serum parameters, C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.",

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AU - Akahori, Hiromichi

AU - Shibuya, Kazunori

AU - Obuchi, Masako

AU - Nishizawa, Yoshito

AU - Tsuji, Akio

AU - Kabaya, Koji

AU - Kusaka, Masaru

AU - Ohashi, Hideya

AU - Tsumura, Haruhiko

AU - Kato, Takashi

AU - Miyazaki, Hiroshi

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N2 - We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey's serum once each day from day 1 to day 2.8. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTP0-treated animals exhibited no significant-changes in several serum parameters, C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

AB - We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 μg/kg/d or monkey's serum once each day from day 1 to day 2.8. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTP0-treated animals exhibited no significant-changes in several serum parameters, C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

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Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia

Abstract

Keywords

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