title: Eltrombopag restores trilineage hematopoiesis in refractory severe aplastic anemia that can be sustained on discontinuation of drug.
abstract: About a quarter of patients with severe aplastic anemia remain pancytopenic despite immunosuppressive therapy. We have previously demonstrated that eltrombopag has efficacy in this setting with 44% (11/25) of patients having clinically significant hematologic responses. We now report safety and efficacy data on a further 18 patients and long-term follow-up on the entire cohort of 43 patients. The overall response rate was 17 of 43 patients (40%) at 3 to 4 months, including tri- and bilineage responses. The majority of patients who remained on eltrombopag in an extension study (14/17) continued to show improvement, and 7 eventually had significant increases in neutrophil, red cell, and platelet lineages. Five patients with robust near-normalization of blood counts had drug discontinued at a median of 28.5 months after entry (range, 9-37 months), and all maintained stable counts a median of 13 months (range, 1-15 months) off eltrombopag. Eight patients, including 6 nonresponders and 2 responders, developed new cytogenetic abnormalities on eltrombopag, including 5 with chromosome 7 loss or partial deletion. None evolved to acute myeloid leukemia to date. Eltrombopag is efficacious in a subset of patients with aplastic anemia refractory to immunosuppressive therapy, with frequent multilineage responses and maintenance of normalized hematopoiesis off treatment. This study is registered at www.clinicaltrials.gov as #NCT00922883.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD;
authors.forename: Ronan
authors.initials: R
authors.lastname: Desmond
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Townsley
authors.forename: Bogdan
authors.initials: B
authors.lastname: Dumitriu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Olnes
authors.forename: Phillip
authors.initials: P
authors.lastname: Scheinberg
authors.forename: Margaret
authors.initials: M
authors.lastname: Bevans
authors.forename: Ankur R
authors.initials: AR
authors.lastname: Parikh
authors.forename: Kinneret
authors.initials: K
authors.lastname: Broder
authors.forename: Katherine R
authors.initials: KR
authors.lastname: Calvo
authors.forename: Colin O
authors.initials: CO
authors.lastname: Wu
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Cynthia E
authors.initials: CE
authors.lastname: Dunbar
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D001565:Benzoates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects / Q000473:pathology; D060965:Clonal Evolution / Q000187:drug effects / Q000235:genetics; D005260:Female; D006401:Hematologic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011720:Pyrazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D055815:Young Adult
chemical_list: D001565:Benzoates; D006401:Hematologic Agents; D006834:Hydrazines; D007166:Immunosuppressive Agents; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C520809:eltrombopag