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 language||English (US)|
|Number of pages||9|
|Journal||Annals of internal medicine|
|State||Published - May 1 1997|
ASJC Scopus subject areas
- Internal Medicine