Response: Thrombocytosis in low-risk ET patients

Response

We thank Dr Tefferi for the comment to our work and are glad to answer his questions. First, the threshold of platelet count recommended for starting a cytoreductive treatment in otherwise “low-risk” essential thrombocythemia (ET) patients is a controversial issue, so that experts' opinions and clinical practice have changed over time. The Italian guidelines¹  reflect the consensus of experts based on the limited information available in 2004, when it was decided to follow a precautionary principle to treat patients with high platelet count, particularly if they had associated cardiovascular risk factors. However, the lack of controlled study and further published data on this topic, including Tefferi et al's letter in Blood,²  addressed the clinical practice of many Centers, including ours, to limit or even avoid treating ET patients on the basis of high platelet count. As a matter of fact, only 20 patients (2%) included in our analysis were “low-risk” patients given short-term cytoreduction because of platelet count more than 1500 × 10⁹/L. Second, we did not include in our paper a separate analysis restricted to “low-risk” untreated patients because we had only 58 incidents of thrombotic events in this subgroup and, therefore, the risk estimates were not as accurate as needed. We performed a multivariable analysis (adjusted for center, sex, hemoglobin, leukocyte count, and low-dose aspirin) exploring the relationship between major thrombosis and platelet number in this untreated group. Results have shown a hazard ratio (HR) of 0.65 (95% confidence interval [CI] 0.31-1.25; P = .15) for patients with a platelet count more than 1000 × 10⁹/L. Thus, a clear, albeit not significant, trend toward “more platelets, less thrombosis” can be observed also in these patients. Overall, we are happy to share with Dr Tefferi the belief that thrombocytosis, per se, should not be taken as a good reason to give cytotoxic chemotherapy to otherwise low-risk ET patients.