title: Eltrombopag and improved hematopoiesis in refractory aplastic anemia.
abstract: BACKGROUND
  Severe aplastic anemia, which is characterized by immune-mediated bone marrow hypoplasia and pancytopenia, can be treated effectively with immunosuppressive therapy or allogeneic transplantation. One third of patients have disease that is refractory to immunosuppression, with persistent, severe cytopenia and a profound deficit in hematopoietic stem cells and progenitor cells. Thrombopoietin may increase the number of hematopoietic stem cells and progenitor cells.
  
  
  METHODS
  We conducted a phase 2 study involving patients with aplastic anemia that was refractory to immunosuppression to determine whether the oral thrombopoietin mimetic eltrombopag (Promacta) can improve blood counts. Twenty-five patients received eltrombopag at a dose of 50 mg, which could be increased, as needed, to a maximum dose of 150 mg daily, for a total of 12 weeks. Primary end points were clinically significant changes in blood counts or transfusion independence. Patients with a response continued to receive eltrombopag.
  
  
  RESULTS
  Eleven of 25 patients (44%) had a hematologic response in at least one lineage at 12 weeks, with minimal toxic effects. Nine patients no longer needed platelet transfusions (median increase in platelet count, 44,000 per cubic millimeter). Six patients had improved hemoglobin levels (median increase, 4.4 g per deciliter); 3 of them were previously dependent on red-cell transfusions and no longer needed transfusions. Nine patients had increased neutrophil counts (median increase, 1350 per cubic millimeter). Serial bone marrow biopsies showed normalization of trilineage hematopoiesis in patients who had a response, without increased fibrosis. Monitoring of immune function revealed no consistent changes.
  
  
  CONCLUSIONS
  Treatment with eltrombopag was associated with multilineage clinical responses in some patients with refractory severe aplastic anemia. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00922883.).
authors: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Matthew J
authors: MJ
authors: Olnes
authors: Phillip
authors: P
authors: Scheinberg
authors: Katherine R
authors: KR
authors: Calvo
authors: Ronan
authors: R
authors: Desmond
authors: Yong
authors: Y
authors: Tang
authors: Bogdan
authors: B
authors: Dumitriu
authors: Ankur R
authors: AR
authors: Parikh
authors: Susan
authors: S
authors: Soto
authors: Angelique
authors: A
authors: Biancotto
authors: Xingmin
authors: X
authors: Feng
authors: Jay
authors: J
authors: Lozier
authors: Colin O
authors: CO
authors: Wu
authors: Neal S
authors: NS
authors: Young
authors: Cynthia E
authors: CE
authors: Dunbar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000188:drug therapy* / Q000473:pathology; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000166:cytology; D002908:Chronic Disease; D004351:Drug Resistance; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; D011720:Pyrazoles; C520809:eltrombopag