title: Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations.
abstract: Platelet transfusion is currently the primary medical treatment for reducing thrombocytopenia in patients with inherited thrombocytopenias. To evaluate whether stimulating megakaryopoiesis could increase platelet count in these conditions, we treated patients with a severe thrombocytopenia induced by MYH9 mutations (MYH9-related disease) with a nonpeptide thrombopoietin receptor agonist, eltrombopag. Twelve adult patients with MYH9-RD and platelet counts of less than 50 × 10(9)/L received 50 mg of eltrombopag orally per day for 3 weeks. Patients who achieved a platelet count higher than 150 × 10(9)/L stopped therapy, those with 100 to 150 platelets × 10(9)/L continued treatment at the same eltrombopag dose for 3 additional weeks, while those with less than 100 platelets × 10(9)/L increased the eltrombopag dose to 75 mg for 3 weeks. Major responses (platelet count of at least 100 × 10(9)/L or 3 times the baseline value) were obtained in 8 patients, minor responses (platelet counts at least twice the baseline value) in 3. One patient did not respond. Bleeding tendency disappeared in 8 of 10 patients with bleeding symptoms at baseline. Mild adverse events were reported in 2 patients. The availability of thrombopoietin mimetics opened new prospects in the treatment of inherited thrombocytopenias. This study is registered at www.clinicaltrials.gov as NCT01133860 (European Union Drug Regulating Authorities Clinical Trials number 2008-001903-42).
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Policlinico San Matteo Foundation-University of Pavia, Pavia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pecci
authors.forename: Paolo
authors.initials: P
authors.lastname: Gresele
authors.forename: Catherine
authors.initials: C
authors.lastname: Klersy
authors.forename: Anna
authors.initials: A
authors.lastname: Savoia
authors.forename: Patrizia
authors.initials: P
authors.lastname: Noris
authors.forename: Tiziana
authors.initials: T
authors.lastname: Fierro
authors.forename: Valeria
authors.initials: V
authors.lastname: Bozzi
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Mezzasoma
authors.forename: Federica
authors.initials: F
authors.lastname: Melazzini
authors.forename: Carlo L
authors.initials: CL
authors.lastname: Balduini
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001565:Benzoates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D006834:Hydrazines / Q000008:administration & dosage*; D008297:Male; D020409:Molecular Motor Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D018995:Myosin Heavy Chains / Q000235:genetics*; D010974:Platelet Aggregation; D010976:Platelet Count; D011720:Pyrazoles / Q000008:administration & dosage*; D053628:Receptors, Thrombopoietin / Q000819:agonists; D015996:Survival Rate; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D001565:Benzoates; D006834:Hydrazines; C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D011720:Pyrazoles; D053628:Receptors, Thrombopoietin; D018995:Myosin Heavy Chains; C520809:eltrombopag