title: Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status.
abstract: BACKGROUND
  Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial.
  
  
  OBJECTIVE
  To assess the impact of mutational status in response rates and development of adverse events during long-term use of anagrelide.
  
  
  METHODS
  We retrospectively evaluated 67 patients with essential thrombocythemia treated with anagrelide during 68 (4-176) months.
  
  
  RESULTS
  Mutational frequencies were 46.3%, 28.3%, and 1.5% for JAK2V617F, CALR and MPL mutations. Anagrelide yielded a high rate of hematologic responses, which were complete in 49.25% and partial in 46.25%, without differences among molecular subsets. The rate of thrombosis during treatment was one per 100 patient-years, without excess bleeding. Anemia was the major adverse event, 30.3% at 5-yr follow-up, being more frequent in CALR(+) (P < 0.05). Myelofibrotic transformation developed in 14.9% (12.9%, 21%, and 12.5% in JAK2V617F(+), CALR(+), and triple-negative patients, respectively, P = NS) and those treated >60 months were at higher risk, OR (95% CI) 9.32 (1.1-78.5), P < 0.01, indicating the need for bone marrow monitoring during prolonged treatment.
  
  
  CONCLUSIONS
  Although CALR(+) patients were at higher risk of developing anemia, anagrelide proved effective among all molecular subsets, indicating that mutational status does not seem to represent a major determinant of choice of cytoreductive treatment among essential thrombocythemia therapies.
authors.affiliation: Clínica Médica , Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: María J
authors.initials: MJ
authors.lastname: Mela Osorio
authors.affiliation: Clínica Médica , Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Ferrari
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Nora P
authors.initials: NP
authors.lastname: Goette
authors.affiliation: Genómica , Laboratorio Stamboulian, Buenos Aires, Argentina.
authors.forename: Marina I
authors.initials: MI
authors.lastname: Gutierrez
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Glembotsky
authors.affiliation: Genómica , Laboratorio Stamboulian, Buenos Aires, Argentina.
authors.forename: Ana C
authors.initials: AC
authors.lastname: Maldonado
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Paola R
authors.initials: PR
authors.lastname: Lev
authors.affiliation: Anatomía Patológica, Instituto de Investigaciones Médicas Alfredo Lanari, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Clarisa
authors.initials: C
authors.lastname: Alvarez
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Korin
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Rosana F
authors.initials: RF
authors.lastname: Marta
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Felisa C
authors.initials: FC
authors.lastname: Molinas
authors.affiliation: Hematología Investigación , Instituto de Investigaciones Médicas Alfredo Lanari , Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET) , Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Paula G
authors.initials: PG
authors.lastname: Heller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology / Q000473:pathology; D037282:Calreticulin / Q000235:genetics* / Q000276:immunology; D002648:Child; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D055728:Primary Myelofibrosis / Q000209:etiology / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D053628:Receptors, Thrombopoietin / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies; D013920:Thrombocythemia, Essential / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: C576483:CALR protein, human; D037282:Calreticulin; D010975:Platelet Aggregation Inhibitors; D011799:Quinazolines; D053628:Receptors, Thrombopoietin; C082218:MPL protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C021139:anagrelide
keywords: Essential thrombocythemia; anagrelide; calreticulin; janus kinase 2