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


METHODS
Phase I and II clinical cohort study.


METHODS
The University of Texas M.D. Anderson Cancer Center, Houston, Texas.


METHODS
12 patients with sarcoma who had high risk for severe chemotherapy-induced thrombocytopenia.


METHODS
A single intravenous dose of thrombopoietin (0.3 to 2.4 micrograms/kg of body weight) 3 weeks before chemotherapy.


METHODS
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.
Vadhan-Raj
S
S
University of Texas M.D. Anderson Cancer Center, Houston, USA.
Murray
L J
LJ
Bueso-Ramos
C
C
Patel
S
S
Reddy
S P
SP
Hoots
W K
WK
Johnston
T
T
Papadopolous
N E
NE
Hittelman
W N
WN
Johnston
D A
DA
Yang
T A
TA
Paton
V E
VE
Cohen
R L
RL
Hellmann
S D
SD
Benjamin
R S
RS
Broxmeyer
H E
HE
D000906:Antibodies / Q000097:blood; D000970:Antineoplastic Agents / Q000009:adverse effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001853:Bone Marrow / Q000187:drug effects; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D008533:Megakaryocytes / Q000187:drug effects / Q000378:metabolism*; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy; D010976:Platelet Count / Q000187:drug effects; D011003:Ploidies; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D013926:Thrombopoietin / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000906:Antibodies; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D013926:Thrombopoietin