Treatment of essential thrombocythemia with special emphasis on leukemogenic risk

Acute leukemia and myelodysplastic syndromes are rare, but almost invariabl y fatal, evolutions of essential thrombocythemia (ET). Three major factors are associated with blastic transformation: cytogenetic abnormalities, myel ofibrotic features, and the use of cytotoxic agents. Hematological malignan cies have been reported in ET patients after treatment with alkylating agen ts, such as busulphan, as well as other cytoreductive drugs, such as hydrox yurea. Concerns about leukemogenicity have led some to suggest limiting the indications of these drugs to patients at higher risk of bleeding and thro mbosis. Major risk factors for thrombosis are age above 60 years and a prev ious thrombotic event, whereas an increased bleeding tendency has been repo rted with platelet counts in excess of 1000-1500 x 10(9)/1. No myelosuppres sive therapy is recommended for younger patients if they are asymptomatic o r their platelet counts are below 1500 x 10(9)/1. The threshold of 1500 x 1 0(9)/1 is controversial, however, and cytoreduction can be considered when platelets are above 1000 x 10(9)/1 or in the presence of risk factors for c ardiovascular disease. In the presence of thrombotic events or extreme thro mbocytosis, young ET patients can be managed with cytoreductive agents theo retically devoid of leukemogenic risk, such as a-interferon or anagrelide. Nevertheless, the mutagenic risk of anagrelide has not been investigated in long-term follow-up studies, and the ultimate place of these 'new' drugs i n the management of ET patients remains to be established in prospective an d controlled clinical trials.