The molecular response rate was 38% in ET and 54% in PV, being complete (undetectable JAK2 V617F) in 6% and 14%, respectively. The JAK2 V617F mutant allele burden continued to decrease with no clear evidence for a plateau. The tolerability was good with only 10% of patients taken off study for drug-related adverse

events.58 Thus, this agent may have an important role in the treatment of PV and other clonal MPN. Busulphan is a cell cycle non-specific alkylating agent of the class of alkyl sulfonates. When used at low doses (usually, 2–4 mg daily) it can produce prolonged control of hematologic parameters in patients with PV or ET with relative safe and easy management. ELN recommends this drug in elderly patients.12 The leukemogenic risk associated with low-dose busulphan Veliparib solubility dmso is probably small. On the contrary the sequential use of busulphan and hydroxyurea resulted in a significant increase in the risk of second malignancies, including leukemias.[34] and [40] By definition, children with ET are a population with low vascular risk unless a major thrombotic or hemorrhagic event has occurred. ELN recommends to prescribe cytoreductive

drugs in children as a last resort.12 In rare cases that need treatment to prevent recurrences after a severe vascular complication, the selection of a cytotoxic or cytoreductive agent should be done after discussion with the child and the parents. HU and Interferon-alpha are first line therapies. The long-term leukemogenicity of HU may be a special concern for children, although none Copanlisib manufacturer of the pediatric patients treated with this agent have yet undergone malignant transformation.59 Adverse effects of interferon alpha such as flu-like syndrome, neuropsychiatric symptoms, and autoimmune phenomena can be particularly dangerous for children. Anagrelide is not licensed as first-line therapy for ET in Europe and ELN group recommends this drug as second line

therapy.12 The use of aspirin in children less than 12 years of age should be prescribed with caution because of the risk of Reye’s syndrome.60 Overall, according to ELN experts, there are insufficient data to recommend a specific agent in children, and the choice should be individually tailored.[12] and [61] In conclusion, in line with the ELN recommendations,12 first line therapy in all patients with PV Nintedanib (BIBF 1120) (Table 4) should be phlebotomy to maintain the hematocrit less than 45%, and low-dose aspirin (75–100 mg). Cytoreduction is strongly indicated in high risk cases defined by age and previous major vascular events. Poor tolerance to or high need of phlebotomy, symptomatic or progressive splenomegaly, severe disease related symptoms, platelet counts greater than 1500 × 109/L or progressive leukocytosis are other indications to cytoreduction. Either HU or IFN-alpha are the first-line therapy at any age. Intermittent busulphan may be considered in elderly patients.