Efficacy, safety and tolerability of anagrelide in the treatment of essential thrombocythaemia

Background: Essential thrombocythaemia (ET) has an associated risk of thrombotic and haemorrhagic complications, which can be minimised by control of the platelet count. Anagrelide selectively lowers the platelet count, however, there is little Australasian experience with its use and scant data on symptom control. Aims: To evaluate the efficacy of anagrelide for platelet reduction and symptom control in a broad cohort of patients with well-defined ET, and to determine the safety and tolerability in such a population. Methods: Seventeen patients with ET and a platelet count >600x10(9)/L were prospectively enrolled. The evaluable four males and 12 females with a median age of 58 years (range 14-79) included ten patients (63%) previously treated with two or more agents and 12 patients (75%) who had failed other therapies. The median follow-up was seven months (range 15 days to 36 months). Results: Anagrelide, in an average dose of 1.9 mg/day, reduced the platelet count from a mean of 728x10(9)/L (95% CI 611-845x10(9)/L) to 412x10(9)/L (95% CI 319-504x10(9)/L) (p<0.001) and maintained it at this level. Fourteen patients (88%) had a platelet reduction to <600x10(9)/L. All symptomatic patients had improvement in symptoms attributable to thrombocythaemia. There were three haemorrhagic and three thrombotic episodes in a total of three patients (19%), including one death from an intracerebral haemorrhage. Six patients (37%) were removed from therapy due to toxicity after a median of 151 days. Side effects included palpitations, abdominal pain and cough. Conclusions: Anagrelide is efficacious and safe in ET, both for platelet and symptom control. Minor side effects are common, however, tend to occur early and resolve spontaneously in most cases.