Ten/fifteen-year survival, leukemic transformation and fibrotic progression rates were significantly worse in early/prefibrotic PMF vs ET. However thrombosis rates were similar between the two groups. These results validate the clinical relevance of strict adherence to WHO criteria in the diagnosis of ET. In connection to this, useful GSK J4 price information

is expected from the Anahydret trial.49 Anahydret is a randomized single blind international multicenter phase III study designed to evaluate the non-inferiority of anagrelide vs HU in 258 high risk ET patients diagnosed according to the 2008 WHO diagnostic criteria. This classification, at variance of PVSG criteria required in the PT-1 trial, included a more homogenous category of patients excluding those with early myelofibrosis who, at diagnosis, present different hematological and clinical features in comparison with WHO-ET. Moreover, contrary to PT-1 enrolling

criteria that included all comers with ET, these were de novo diagnosed and cytotoxic therapy naïve patients. During the whole study period, 11 major ET‐related complications occurred in the anagrelide group (5 arterial events, 2 venous thrombotic complications Doramapimod manufacturer and 4 bleedings) and 12 major events were seen in the hydroxyurea arm (5 arterial events, 5 venous thrombotic events and 2 bleedings). Transformations to myelofibrosis were not reported. This study provides preliminary evidence for non-inferiority of anagrelide

compared to HU in the first line treatment of ET diagnosed according to the WHO classification. However, compared to PT-1, the number of patients enrolled was small, duration of follow-up relatively short and considerably fewer end-point events were recorded. It is therefore questionable whether this study has the statistical power to detect the differences observed in the PT-1 study. Therefore, anagrelide does appear to provide partial protection from thrombosis, particularly in JAK2 V617F Alectinib manufacturer negative ET patients, and may be suitable as second line therapy for patients in whom hydroxyurea is inadequate or not tolerated.[17] and [50] In Europe, anagrelide is licensed only for patients with ET who are refractory or intolerant to first-line therapy with hydroxyurea, according to the ELN criteria.44 On the contrary, anagrelide has been approved by the Food and Drug Administration as a first-line agent for the control of thrombocytosis associated with MPN. IFN-alpha was considered for the treatment of patients with MPN since this agent suppresses the proliferation of hematopoietic progenitors, has a direct inhibiting effect on bone marrow fibroblast progenitor cells, and antagonizes the action of platelet-derived growth factor, transforming growth factor-beta and other cytokines, which may be involved in the development of myelofibrosis.