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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3526.
CORRESPONDENCE Platelet count in essential thrombocythemia: the more the better?To the editor:To date, drug therapy in essential thrombocythemia (ET) has not been shown to positively influence the risk of leukemic or fibrotic transformation. In contrast, an often-cited controlled study1 has demonstrated the antithrombotic value of hydroxyurea therapy in high-risk patients. In this particular study, "high-risk" disease was appropriately defined by the presence of advanced age (> 60 years) and/or history of thrombosis and did not include patients with a platelet count of more than 1500 x 109/L.1 There is no other "no-treatment arm" controlled study in ET that either supports the benefit of cytoreductive therapy or indicates a higher incidence of thrombotic complications in otherwise "low-risk" patients with extreme thrombocytosis. Similarly, there is limited information, in terms of hard evidence, that supports the theoretically appealing2 association between extreme thrombocytosis and non–aspirin associated bleeding.3 Instead, a recent retrospective study of low-risk ET patients with extreme thrombocytosis showed no benefit for cytoreductive therapy in terms of either thrombotic or hemorrhagic complications.3 Despite the above facts, the presence of extreme thrombocytosis in ET is considered by many as a recipe for vascular catastrophe and hence as an indication for cytoreductive therapy. This unsubstantiated concept has also been used to promote the therapeutic use of anagrelide, a platelet-specific cytoreductive agent. These are some of the reasons why the recent Blood paper by Carobbio et al has major relevance to current clinical practice.4 Among 1063 patients with ET, the authors demonstrated a significantly lower risk of thrombosis in patients presenting with extreme thrombocytosis, an effect that was independent of both age and thrombosis history. However, while I am comforted by this additional evidence for the lack of a direct correlation between extreme thrombocytosis and the risk of thrombosis in ET, I believe that the authors' claim for an inverse correlation requires further clarification. To begin with, the authors clearly state in their paper that low-risk versus high-risk disease was distinguished by the absence in the former and presence in the latter of age 60 years or older and/or thrombosis history, and that low-risk patients were followed without chemotherapy. Although I personally subscribe to this management strategy, I find the authors' statement contrary to their previously published guidelines for the treatment of ET, where they recommended the use of cytoreductive drugs in low-risk patients with a platelet count of either more than 1500 x 109/L, or 1000 to 1500 x 109/L in the presence of cardiovascular symptoms.4 This is an important point that needs to be clarified, because the latter scenario would lead to a higher likelihood for "low-risk" patients with extreme thrombocytosis to be on cytoreductive treatment. Adjusting thrombosis risk for chemotherapy in such a setting does not necessarily address the potential confounding effect of treatment; it is often difficult to determine in a retrospective study whether or not treatment was instituted for primary or secondary prevention of thrombosis. Furthermore, from a therapeutically relevant standpoint, it would be most useful if the authors shared the outcome of their analysis restricted to "low-risk" patients. Authorship Conflict-of-interest disclosure: The author declares no competing financial interests. Correspondence: Ayalew Tefferi, MD, Division of Hematology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905; e-mail: tefferi.ayalew{at}mayo.edu.
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