Recombinant human thrombopoietin in combination with granulocyte colony- stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy

George Somlo, Irena Sniecinski, Anna Ter Veer, Jeffrey Longmate, Gaylord Knutson, Stanimir Vuk-Pavlovic, Ravi Bhatia, Warren Chow, Lucille Leong, Robert Morgan, Kim Margolin, James Raschko, Stephen Shibata, Merry Tetef, Yun Yen, Stephen Forman, Dennie Jones, Mark Ashby, Gwen Fyfe, Susan HellmannJames H. Doroshow

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 μg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 μg/kg on days -3, -1, and 1, or 0.6 μg/kg on days -1 and 1. G- CSF, 5 μg/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34+ cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 106/kg (range, 1.3 to 17.6) versus 0.8 x 106/kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 x 106 CD34+ cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P = .001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P = .0001) and platelet recovery (day 9 v 10, P = .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and platelet (4 v 5, P = .02) transfusions were needed compared with G- CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 μg/kg, rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.

Original languageEnglish
Pages (from-to)2798-2806
Number of pages9
JournalBlood
Volume93
Issue number9
Publication statusPublished - May 1 1999
Externally publishedYes

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Thrombopoietin
Chemotherapy
Granulocyte Colony-Stimulating Factor
Platelets
Blood Cells
Blood
Stem Cells
Blood Platelets
Drug Therapy
Recovery
Blood Component Removal
Breast Neoplasms
Platelet Count
Granulocytes
Human Activities
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Recombinant human thrombopoietin in combination with granulocyte colony- stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy. / Somlo, George; Sniecinski, Irena; Ter Veer, Anna; Longmate, Jeffrey; Knutson, Gaylord; Vuk-Pavlovic, Stanimir; Bhatia, Ravi; Chow, Warren; Leong, Lucille; Morgan, Robert; Margolin, Kim; Raschko, James; Shibata, Stephen; Tetef, Merry; Yen, Yun; Forman, Stephen; Jones, Dennie; Ashby, Mark; Fyfe, Gwen; Hellmann, Susan; Doroshow, James H.

In: Blood, Vol. 93, No. 9, 01.05.1999, p. 2798-2806.

Research output: Contribution to journalArticle

Somlo, G, Sniecinski, I, Ter Veer, A, Longmate, J, Knutson, G, Vuk-Pavlovic, S, Bhatia, R, Chow, W, Leong, L, Morgan, R, Margolin, K, Raschko, J, Shibata, S, Tetef, M, Yen, Y, Forman, S, Jones, D, Ashby, M, Fyfe, G, Hellmann, S & Doroshow, JH 1999, 'Recombinant human thrombopoietin in combination with granulocyte colony- stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy', Blood, vol. 93, no. 9, pp. 2798-2806.
Somlo, George ; Sniecinski, Irena ; Ter Veer, Anna ; Longmate, Jeffrey ; Knutson, Gaylord ; Vuk-Pavlovic, Stanimir ; Bhatia, Ravi ; Chow, Warren ; Leong, Lucille ; Morgan, Robert ; Margolin, Kim ; Raschko, James ; Shibata, Stephen ; Tetef, Merry ; Yen, Yun ; Forman, Stephen ; Jones, Dennie ; Ashby, Mark ; Fyfe, Gwen ; Hellmann, Susan ; Doroshow, James H. / Recombinant human thrombopoietin in combination with granulocyte colony- stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy. In: Blood. 1999 ; Vol. 93, No. 9. pp. 2798-2806.
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abstract = "Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 μg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 μg/kg on days -3, -1, and 1, or 0.6 μg/kg on days -1 and 1. G- CSF, 5 μg/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34+ cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 106/kg (range, 1.3 to 17.6) versus 0.8 x 106/kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 x 106 CD34+ cells/kg was procured following a single apheresis procedure in 61{\%} of the rhTPO and G-CSF-mobilized group versus 10{\%} of G-CSF-mobilized patients (P = .001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P = .0001) and platelet recovery (day 9 v 10, P = .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and platelet (4 v 5, P = .02) transfusions were needed compared with G- CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100{\%} and the platelet content of PBPC products by 60{\%} to 110{\%} on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 μg/kg, rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.",
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T1 - Recombinant human thrombopoietin in combination with granulocyte colony- stimulating factor enhances mobilization of peripheral blood progenitor cells, increases peripheral blood platelet concentration, and accelerates hematopoietic recovery following high-dose chemotherapy

AU - Somlo, George

AU - Sniecinski, Irena

AU - Ter Veer, Anna

AU - Longmate, Jeffrey

AU - Knutson, Gaylord

AU - Vuk-Pavlovic, Stanimir

AU - Bhatia, Ravi

AU - Chow, Warren

AU - Leong, Lucille

AU - Morgan, Robert

AU - Margolin, Kim

AU - Raschko, James

AU - Shibata, Stephen

AU - Tetef, Merry

AU - Yen, Yun

AU - Forman, Stephen

AU - Jones, Dennie

AU - Ashby, Mark

AU - Fyfe, Gwen

AU - Hellmann, Susan

AU - Doroshow, James H.

PY - 1999/5/1

Y1 - 1999/5/1

N2 - Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 μg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 μg/kg on days -3, -1, and 1, or 0.6 μg/kg on days -1 and 1. G- CSF, 5 μg/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34+ cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 106/kg (range, 1.3 to 17.6) versus 0.8 x 106/kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 x 106 CD34+ cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P = .001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P = .0001) and platelet recovery (day 9 v 10, P = .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and platelet (4 v 5, P = .02) transfusions were needed compared with G- CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 μg/kg, rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.

AB - Lineage-specific growth factors mobilize peripheral blood progenitor cells (PBPC) and accelerate hematopoietic recovery after high-dose chemotherapy. Recombinant human thrombopoietin (rhTPO) may further increase the progenitor-cell content and regenerating potential of PBPC products. We evaluated the safety and activity of rhTPO as a PBPC mobilizer in combination with granulocyte colony-stimulating factor (G-CSF) in 29 breast cancer patients treated with high-dose chemotherapy followed by PBPC reinfusion. Initially, patients received escalating single doses of rhTPO intravenously (IV) at 0.6, 1.2, or 2.4 μg/kg, on day 1. Subsequent patients received rhTPO 0.6 or 0.3 μg/kg on days -3, -1, and 1, or 0.6 μg/kg on days -1 and 1. G- CSF, 5 μg/kg IV or subcutaneously (SC) twice daily, was started on day 3 and continued through aphereses. Twenty comparable, concurrently and identically treated patients (who were eligible and would have been treated on protocol but for the lack of study opening) mobilized with G-CSF alone served as comparisons. CD34+ cell yields were substantially higher with the first apheresis following rhTPO and G-CSF versus G-CSF alone: 4.1 x 106/kg (range, 1.3 to 17.6) versus 0.8 x 106/kg (range, 0.3 to 4.2), P = .0003. The targeted minimum yield of 3 x 106 CD34+ cells/kg was procured following a single apheresis procedure in 61% of the rhTPO and G-CSF-mobilized group versus 10% of G-CSF-mobilized patients (P = .001). In rhTPO and G-CSF mobilized patients, granulocyte (day 8 v 9, P = .0001) and platelet recovery (day 9 v 10, P = .07) were accelerated, and fewer erythrocyte (3 v 4, P = .02) and platelet (4 v 5, P = .02) transfusions were needed compared with G- CSF-mobilized patients. Peripheral blood platelet counts, following rhTPO and G-CSF, were increased by greater than 100% and the platelet content of PBPC products by 60% to 110% on the first and second days of aphereses (P < .0001) with the greatest effect seen with repeated dosing of rhTPO at 0.6 μg/kg, rhTPO is safe and well tolerated as a mobilizing agent before PBPC collection. Mobilization with rhTPO and G-CSF, in comparison to a comparable, nonrandomized G-CSF-mobilized group of patients, decreases the number of apheresis procedures required, may accelerate hematopoietic recovery, and may reduce the number of transfusions required following high-dose chemotherapy for breast cancer.

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