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1 May 1997 | Volume 126 Issue 9 | Pages 673-681
Background: 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.
Author and Article Information
From The University of Texas M.D. Anderson Cancer Center, Houston, Texas; SyStemix, Inc., San Francisco, California; Genentech, Inc., South San Francisco, California; and Indiana University School of Medicine, Indianapolis, Indiana.
ARTICLE
Stimulation of Megakaryocyte and Platelet Production by a Single Dose of Recombinant Human Thrombopoietin in Patients with Cancer
Acknowledgments: The authors thank Duane Bloedow, PhD, and Tauri Senn for their help in pharmacokinetics analysis; Yang Huh, MD, for immunophenotypic analysis; Karin Luens for ploidy analysis; Debbie Sayre and Nancy Hague for technical assistance; and Zenaida Silva for manuscript preparation.
Grant Support: In part by R01 HL56416, R01 HL54037, and P01 HL53586 from the National Heart, Lung, and Blood Institute and by a research grant from Genentech, Inc. (South San Francisco, California).
Requests for Reprints: Saroj Vadhan-Raj, MD, Department of Bioimmunotherapy, Box 002, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
Current Author Addresses: Drs. Vadhan-Raj and Reddy and Ms. Johnston: Department of Bioimmunotherapy, Box 002, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030.
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