Long-Term Evaluation of 205 Patients with Essential Thrombocythemia: Clinical Outcome, Efficacy and Safety with Respect to Different Therapies.
Authors: Vianelli Nicola , deVivo Antonio , Fiacchini Mauro , Lucchesi Alessandro , Giannini Benedetta , Baccarani Michele 
Published: October 2019

Abstract
Essential Thrombocythemia (ET) is a myeloproliferative disorder associated with persistent thrombocytosis. The main clinical features are recurrent thrombotic and/or hemorrhagic events, involving both the arterial and venous systems. Data concerning the role of platelet-lowering agents to prevent thrombotic and hemorrhagic events are not conclusive, despite the risk associated to the use of some of them as hydroxyurea (HU) or alkylating agents like busulfan (BU), to induce a leukemic transformation or solid malignancy. We report here our experience, on 205 (M 78, F 127) consecutive ET patients (pts) referred to our Institute between January 1977 and December 2003, with a median follow-up of 76 months (4–318). Median age at diagnosis was 66 (15–91) years; median platelet (PLT) number was 780 (465–3700) x109/L. One hundred and ninety-five pts (95%) were considered at high risk for thrombosis. One hundred and eighty of them (92.3%) were treated with platelet-lowering agents: HU (82 pts), BU (39 pts), HU+BU (37 pts), IFNa (6 pts), HU+IFNa (10 pts), BU+IFNa (2 pts) or HU+BU+IFNa (4 pts). In 30/180 (16.7%) and 124/180 (68.9%) pts the treatments were able to maintain the PLT number <400x109/L (Complete remission) and 400–600x109/L (Partial remission), respectively, for at least 2/3 of their follow-up. Only three pts withdrawn HU or BU for toxicity. A total of 192 (93.6%) pts received antiplatelet agents (121 Aspirin, 34 Ticlopidine, 37 others) for a median period of 53(1–318) months; in 42 pts this therapy was withdrawn, in most cases after gaining control of the platelet count (PLT <600x109/L). During follow-up we registered 33 thrombotic events in 21 (10.2%) pts, and 22 hemorrhagic events in 20 (9.8%) pts, while dizziness, headache and other symptoms due to microvascular disturbance were present in 88 pts. Patients who received both HU and BU consecutively developed a significantly higher number of thrombotic events, compared to pts who received a single drug (p=0.004); this could be explained by the difficult control of the disease in this subgroup of pts. Previous thrombotic event, age and platelet number at diagnosis, thrombocytosis control during follow-up and presence of one or more common cardiovascular risk factors were evaluated in order to establish any correlation with thrombotic risk. Only the first two factors resulted significant. Blastic tranformations, myelofibrosis evolution and solid malignancy occurred in 2(1.0%), 4(1.9%) and 8(3.9%) pts, respectively. The two pts who showed blastic transformation were treated with a particularly high total dose of HU (3039500mg) if compared to the median dose administered (462000mg) or with the sequential association of HU and BU. No strict correlation was observed between the 8 pts who developed a solid malignancy and the therapy administered. The overall survival expressed by the Kaplan-Meier curve was approximately 85% at 12 years after diagnosis, that is similar to the life expectancy of normal population. In conclusion, in our experience HU and BU resulted effective with neglegible toxicity in controlling thrombocytosis in ET pts. Only previous thrombosis and older age at diagnosis significantly increase the risk of thrombotic event during follow-up. The ET blastic transformation seems to be related to the HU+BU association or to a higher total HU dose administered.