title: What is the potential for thrombopoietic agents in acute leukemia?
abstract: In the 16 years since thrombopoietin was identified and cloned, much has been learned about its biochemistry, how it is regulated, and its involvement in a wide range of functions in a variety of cell lineages. The first generation of recombinant human thrombopoietins, rHuTPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), were shown to increase platelet counts in patients with immune thrombocytopenia, in platelet apheresis donors, and in patients receiving nonmyeloablative chemotherapy. Their effects in patients with acute myeloid leukemia (AML) showed no benefit at a wide range of doses and schedules. The two second-generation TPO mimetics approved by the US Food and Drug Administration (FDA) for the treatment of ITP, romiplostim and eltrombopag, are now being studied in a number of thrombocytopenic disorders including those due to chemotherapy and hepatitis C. Since romiplostim is comparable to the first-generation recombinant thrombopoietins, it may not be beneficial in AML treatment; however, given its novel mechanism of action, eltrombopag may be a TPO potentiator and if given at the proper time during chemotherapy, may enable AML patients to recover platelet counts sooner.
authors: Harvard Medical School, Massachusetts General Hospital, Yawkey, Boston, MA 02114, USA. kuter.david@mgh.harvard.edu
authors: David J
authors: DJ
authors: Kuter
mesh_terms: D000328:Adult; D001565:Benzoates / Q000008:administration & dosage* / Q000627:therapeutic use; D001792:Blood Platelets / Q000166:cytology / Q000276:immunology*; D002986:Clinical Trials as Topic; D060830:Consolidation Chemotherapy / Q000379:methods*; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage* / Q000627:therapeutic use; D015470:Leukemia, Myeloid, Acute / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D018716:Molecular Mimicry; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011720:Pyrazoles / Q000008:administration & dosage* / Q000627:therapeutic use; D011961:Receptors, Fc / Q000008:administration & dosage / Q000627:therapeutic use; D053628:Receptors, Thrombopoietin / Q000819:agonists / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012074:Remission Induction / Q000379:methods; D013921:Thrombocytopenia / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D034061:Thrombopoiesis / Q000187:drug effects* / Q000276:immunology; D013926:Thrombopoietin / Q000008:administration & dosage / Q000378:metabolism* / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; D011961:Receptors, Fc; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C103117:polyethylene glycol-recombinant human megakaryocyte growth and development factor; D011092:Polyethylene Glycols; D013926:Thrombopoietin; C488777:romiplostim; C520809:eltrombopag