Long-term follow-up of essential thrombocythemia patients treated with anagrelide: subgroup analysis according to JAK2/CALR/MPL mutational status

Eur J Haematol. 2016 Apr;96(4):435-42. doi: 10.1111/ejh.12614. Epub 2015 Jul 19.

Abstract

Background: Anagrelide represents a treatment option for essential thrombocythemia, although its place in therapy remains controversial.

Aim: 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.

Conclusion: 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.

Keywords: Essential thrombocythemia; anagrelide; calreticulin; janus kinase 2.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / etiology
  • Anemia / pathology
  • Calreticulin / genetics*
  • Calreticulin / immunology
  • Child
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Janus Kinase 2 / genetics*
  • Janus Kinase 2 / immunology
  • Male
  • Middle Aged
  • Mutation
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Primary Myelofibrosis / etiology
  • Primary Myelofibrosis / pathology
  • Quinazolines / administration & dosage*
  • Quinazolines / adverse effects
  • Receptors, Thrombopoietin / genetics*
  • Receptors, Thrombopoietin / immunology
  • Retrospective Studies
  • Thrombocythemia, Essential / drug therapy*
  • Thrombocythemia, Essential / genetics
  • Thrombocythemia, Essential / immunology
  • Thrombocythemia, Essential / pathology

Substances

  • CALR protein, human
  • Calreticulin
  • Platelet Aggregation Inhibitors
  • Quinazolines
  • Receptors, Thrombopoietin
  • MPL protein, human
  • JAK2 protein, human
  • Janus Kinase 2
  • anagrelide