Anagrelide: a decade of clinical experience with its use for the treatment of primary thrombocythaemia

Abstract

Primary thrombocythaemia (PT) is the most frequent among the rare chronic myeloproliferative disorders. Life expectancy is determined by thromboembolic and haemorrhagic complications, which can be prevented by cytoreductive therapy. For a long time, hydroxyurea has been considered as the therapeutic gold standard. However, hydroxyurea treatment is not lineage-specific, may not be tolerated because of adverse effects (skin, gastrointestinal tract) and is leukaemogenic when sequentially used with other DNA-targeting drugs. Hence, anagrelide was welcomed in 1988 when it was first described as being efficient at normalising elevated platelet counts, specific for megakaryocytes and non-mutagenic. Since then, anagrelide has been approved in the US and Canada (Agrylin), Shire Pharmaceuticals) as well as in Austria and other countries of the EU (Thromboreductin), AOP Orphan Pharmaceuticals). Clinical Phase III trials (PT1 and ANAHYDRET) are underway to directly compare the efficacy and safety of anagrelide and hydroxyurea.

Should Chemotherapy Be Administered for Essential Thrombocythemia (ET) Patients with Leukemic Transformation?

“…Given the long duration of use of these multiple agents and the duration of the primary disease itself, it was not unexpected that this patient had leukemic transformation. The other 2 patients received a combination of HU, anagrelide and interferon (IFN) for 4 and 14 years before LT. To date, anagrelide is not mutagenic 23 and there is no evidence suggesting that it is leukemogenic 22 . Interferon is also not known to be leukemogenic 22 .…”

Comparison between anagrelide and hydroxycarbamide in their activities against haematopoietic progenitor cell growth and differentiation: selectivity of anagrelide for the megakaryocytic lineage

“…6,29 More recently, mainly because of concern about the leukemogenic potential of HC, 32 ANA has also become widely used. 25,26,[33][34][35] However, the choice between the two drugs is often uncertain. Results from a recent clinical trial comparing HC and ANA in high-risk ET patients showed an increased frequency of vascular events and more cases progressing to myelofibrosis in the ANA group.…”

Long-term management of thrombocytosis in essential thrombocythaemia

“…Anagrelide is not mutagenic [74], and there is no known evidence to suggest that it is leukaemogenic [75]. In a longterm retrospective analysis, anagrelide did not result in excess conversion to AML, and no ET patient receiving anagrelide for more than 3 years transformed [64].…”