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

Saroj Vadhan-Raj, Lesley J. Murray, Carlos Bueso-Ramos, Shreyaskumar Patel, Saraswati P. Reddy, William K. Hoots, Taren Johnston, Nicholas E. Papadopoulous, Walter N. Hittelman, Dennis A. Johnston, Timothy A. Yang, Virginia E. Paton, Robert L. Cohen, Susan D. Hellmann, Robert S. Benjamin, Hal Broxmeyer

Research output: Contribution to journalArticle

187 Citations (Scopus)

Abstract

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 languageEnglish
Pages (from-to)673-681
Number of pages9
JournalAnnals of Internal Medicine
Volume126
Issue number9
StatePublished - May 1 1997

Fingerprint

Thrombopoietin
Megakaryocytes
Blood Platelets
Thrombocytopenia
Neoplasms
Bone Marrow
Drug Therapy
Platelet Transfusion
Cell Lineage
Platelet Count
Sarcoma
Half-Life
Cohort Studies
Body Weight
Hemorrhage
Cytokines
Therapeutics
Serum

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. / Vadhan-Raj, Saroj; Murray, Lesley J.; Bueso-Ramos, Carlos; Patel, Shreyaskumar; Reddy, Saraswati P.; Hoots, William K.; Johnston, Taren; Papadopoulous, Nicholas E.; Hittelman, Walter N.; Johnston, Dennis A.; Yang, Timothy A.; Paton, Virginia E.; Cohen, Robert L.; Hellmann, Susan D.; Benjamin, Robert S.; Broxmeyer, Hal.

In: Annals of Internal Medicine, Vol. 126, No. 9, 01.05.1997, p. 673-681.

Research output: Contribution to journalArticle

Vadhan-Raj, S, Murray, LJ, Bueso-Ramos, C, Patel, S, Reddy, SP, Hoots, WK, Johnston, T, Papadopoulous, NE, Hittelman, WN, Johnston, DA, Yang, TA, Paton, VE, Cohen, RL, Hellmann, SD, Benjamin, RS & Broxmeyer, H 1997, 'Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer', Annals of Internal Medicine, vol. 126, no. 9, pp. 673-681.
Vadhan-Raj S, Murray LJ, Bueso-Ramos C, Patel S, Reddy SP, Hoots WK et al. Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. Annals of Internal Medicine. 1997 May 1;126(9):673-681.
Vadhan-Raj, Saroj ; Murray, Lesley J. ; Bueso-Ramos, Carlos ; Patel, Shreyaskumar ; Reddy, Saraswati P. ; Hoots, William K. ; Johnston, Taren ; Papadopoulous, Nicholas E. ; Hittelman, Walter N. ; Johnston, Dennis A. ; Yang, Timothy A. ; Paton, Virginia E. ; Cohen, Robert L. ; Hellmann, Susan D. ; Benjamin, Robert S. ; Broxmeyer, Hal. / Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer. In: Annals of Internal Medicine. 1997 ; Vol. 126, No. 9. pp. 673-681.
@article{861c21922c904ccbacaaf21c74e7f0e1,
title = "Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer",
abstract = "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 = "Saroj Vadhan-Raj and Murray, {Lesley J.} and Carlos Bueso-Ramos and Shreyaskumar Patel and Reddy, {Saraswati P.} and Hoots, {William K.} and Taren Johnston and Papadopoulous, {Nicholas E.} and Hittelman, {Walter N.} and Johnston, {Dennis A.} and Yang, {Timothy A.} and Paton, {Virginia E.} and Cohen, {Robert L.} and Hellmann, {Susan D.} and Benjamin, {Robert S.} and Hal Broxmeyer",
year = "1997",
month = "5",
day = "1",
language = "English",
volume = "126",
pages = "673--681",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",
number = "9",

}

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0030966361&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030966361&partnerID=8YFLogxK

M3 - Article

C2 - 9139552

AN - SCOPUS:0030966361

VL - 126

SP - 673

EP - 681

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 9

ER -