TY - JOUR
T1 - Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer
AU - Vadhan-Raj, Saroj
AU - Murray, Lesley J.
AU - Bueso-Ramos, Carlos
AU - Patel, Shreyaskumar
AU - Reddy, Saraswati P.
AU - Hoots, William K.
AU - Johnston, Taren
AU - Papadopoulous, Nicholas E.
AU - Hittelman, Walter N.
AU - Johnston, Dennis A.
AU - Yang, Timothy A.
AU - Paton, Virginia E.
AU - Cohen, Robert L.
AU - Hellmann, Susan D.
AU - Benjamin, Robert S.
AU - Broxmeyer, Hal E.
PY - 1997/5/1
Y1 - 1997/5/1
N2 - 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.
AB - 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.
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U2 - 10.7326/0003-4819-126-9-199705010-00001
DO - 10.7326/0003-4819-126-9-199705010-00001
M3 - Article
C2 - 9139552
AN - SCOPUS:0030966361
SN - 0003-4819
VL - 126
SP - 673
EP - 681
JO - Annals of internal medicine
JF - Annals of internal medicine
IS - 9
ER -