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

79 Scopus citations

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 (US)
Pages (from-to)2798-2806
Number of pages9
JournalBlood
Volume93
Issue number9
DOIs
StatePublished - May 1 1999

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of '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'. Together they form a unique fingerprint.

  • Cite this

    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., ... Doroshow, J. H. (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, 93(9), 2798-2806. https://doi.org/10.1182/blood.v93.9.2798