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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2493-2494.
CORRESPONDENCE To the editor:Management of extreme thrombocytosis in otherwise low-risk essential thrombocythemia; does number matter?Despite the absence of supporting evidence, many investigators recommend cytoreductive therapy in essential thrombocythemia (ET) on the basis of extreme thrombocytosis alone. Some do so out of anxiety regarding thrombosis; others, with the intent to prevent bleeding complications that have in the past been loosely associated with extreme thrombocytosis in ET.1 In the current study, we took advantage of a large patient cohort with World Health Organization (WHO)–defined2 ET (n = 445), seen at our institution, in order to retrospectively examine the consequences of treatment strategies in 99 consecutive young patients (aged < 60 years) who presented with extreme thrombocytosis (platelet count 1000 x 109/L) that was not, at diagnosis, accompanied by thrombohemorrhagic complications. Among these 99 study patients, 75 received prophylactic cytoreductive therapy; such therapy was deferred until the occurrence of a vascular event in the remaining 24 patients. Treatment decision was based primarily on physician discretion, and the platelet-lowering agents, when used, included hydroxyurea and anagrelide. Table 1 outlines patient characteristics at diagnosis and incidence of major thrombotic or hemorrhagic complications after diagnosis; criteria for major thrombosis and hemorrhage have previously been published.3,4 The 2 subgroups of patients (ie, those receiving or not receiving prophylactic cytoreductive therapy) experienced similar rates of major thrombosis and hemorrhage but displayed significant differences in age distribution as well as follow-up period that might have influenced the overall findings (Table 1). The preponderance of younger patients in the treatment-naive group was not surprising, given the reluctance of many physicians to forego cytoreductive therapy in patients older than 40 years. In contrast, the retrospective nature of the study made it difficult to accurately determine the reasons for the significant variation in follow-up time, although possible explanations include recent shift in practice and/or the less stringent need for follow-up in the absence of active therapy. Regardless, the overall results did not change when statistical analysis either accounted for the difference in follow-up time (Table 1) or was repeated with a cut-off age limit of 40 years; among 41 very young (aged < 40 years) low-risk patients with ET who presented with a platelet count of 1000 x 109/L or higher, the incidences of postdiagnosis major thrombosis (33%; 0.25 per 100 patient-years vs. 18%, 0.17 per 100 patient-years; P = .26) and hemorrhage (8%; 0.06 per 100 patient-years vs. 0%; P = .22) were similar between the 24 patients who were treated with prophylactic cytoreductive therapy and the 17 who did not receive such therapy. Similarly, the exclusion of the 29 patients with microvascular symptoms from the overall analysis did not affect the results (data not shown).
The current study challenges the wisdom of using cytoreductive therapy in young, asymptomatic patients with ET who have extreme thrombocytosis, and underscores the need for validation of such practice in a controlled setting. The study also raises questions regarding the validity of either including5 or excluding6 patients with ET-associated extreme thrombocytosis from clinical trials on the basis of assumed risk of a major hemorrhagic complication.
Correspondence: Ayalew Tefferi, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: tefferi.ayalew{at}mayo.edu.
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