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Ann Intern Med. 1997 May 1;126(9):673-81.

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

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1
University of Texas M.D. Anderson Cancer Center, Houston, USA.

Abstract

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 micrograms/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.

Comment in

PMID:
9139552
[Indexed for MEDLINE]

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