title: Stimulation of megakaryocyte and platelet production by a single dose of recombinant human thrombopoietin in patients with cancer.
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.
  
  
  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.
authors.affiliation: University of Texas M.D. Anderson Cancer Center, Houston, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vadhan-Raj
authors.forename: L J
authors.initials: LJ
authors.lastname: Murray
authors.forename: C
authors.initials: C
authors.lastname: Bueso-Ramos
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: S P
authors.initials: SP
authors.lastname: Reddy
authors.forename: W K
authors.initials: WK
authors.lastname: Hoots
authors.forename: T
authors.initials: T
authors.lastname: Johnston
authors.forename: N E
authors.initials: NE
authors.lastname: Papadopolous
authors.forename: W N
authors.initials: WN
authors.lastname: Hittelman
authors.forename: D A
authors.initials: DA
authors.lastname: Johnston
authors.forename: T A
authors.initials: TA
authors.lastname: Yang
authors.forename: V E
authors.initials: VE
authors.lastname: Paton
authors.forename: R L
authors.initials: RL
authors.lastname: Cohen
authors.forename: S D
authors.initials: SD
authors.lastname: Hellmann
authors.forename: R S
authors.initials: RS
authors.lastname: Benjamin
authors.forename: H E
authors.initials: HE
authors.lastname: Broxmeyer
mesh_terms: 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
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D013926:Thrombopoietin