Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer

Saroj Vadhan-Raj, Lesley J. Murray, Carlos Bueso-Ramos, Shreyaskumar Patel, Saraswati P. Reddy, William K. Hoots, Taren Johnston, Nicholas E. Papadopoulous, Walter N. Hittelman, Dennis A. Johnston, Timothy A. Yang, Virginia E. Paton, Robert L. Cohen, Susan D. Hellmann, Robert S. Benjamin, Hal E. Broxmeyer

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189 Scopus citations

Abstract

Thrombocytopenia is frequently encountered in patients with cancer. It is associated with an increased risk for clinically important bleeding episodes, which increases the demand for platelet transfusion. Objective: To assess hematopoietic response to and clinical tolerance of recombinant human thrombopoietin, a recently cloned novel cytokine. Design: Phase I and II clinical cohort study. Setting: The University of Texas M.D. Anderson Cancer Center, Houston, Texas. Patients: 12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia. Intervention: A single intravenous dose of thrombopoietin (0.3 to 2.4 μg/kg of body weight) 3 weeks before chemotherapy. Measurements: Peripheral blood and bone marrow evaluation before and after thrombopoietin administration. Results: A single dose of thrombopoietin was associated with an increase in platelet counts (mean increase from baseline, 61% to 213%; P = 0.002) in a dose-related manner. This increase began by day 4 in most patients and peaked on a median of day 12. This sustained response was associated with a prolonged serum thrombopoietin half life (20 to 30 hours). The platelets appeared morphologically normal and showed normal aggregation in response to various agonists. Platelet response was accompanied by a dose-related increase in bone marrow megakaryocytes (as much as 4-fold); the expansion of the bone marrow progenitors of myeloid, erythroid, multipotential, and megakaryocytic lineages; and the marked mobilization of progenitors (maximum, 5.7-fold to 10-fold) of multiple cell lineages in the peripheral blood. Treatment was well tolerated, and no serious adverse events occurred. Conclusions: Thrombopoietin, administered as a single dose, is a potent stimulus for prolonged platelet production in humans. It merits further evaluation for the prevention and treatment of thrombocytopenia.

Original languageEnglish (US)
Pages (from-to)673-681
Number of pages9
JournalAnnals of internal medicine
Volume126
Issue number9
DOIs
StatePublished - May 1 1997

ASJC Scopus subject areas

  • Internal Medicine

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    Vadhan-Raj, S., Murray, L. J., Bueso-Ramos, C., Patel, S., Reddy, S. P., Hoots, W. K., Johnston, T., Papadopoulous, N. E., Hittelman, W. N., Johnston, D. A., Yang, T. A., Paton, V. E., Cohen, R. L., Hellmann, S. D., Benjamin, R. S., & Broxmeyer, H. E. (1997). Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Annals of internal medicine, 126(9), 673-681. https://doi.org/10.7326/0003-4819-126-9-199705010-00001