Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV-MF) and essential thrombocythemia (PET-MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of this study was to characterize the mutation landscape, and describe the main clinical correlates and prognostic implications of mutations, in a series of 359 patients with PPV-MF and PET-MF. Compared with PV and ET, the JAK2V617F and CALR mutated allele burden was significantly higher in PPV-MF and/or PET-MF, indicating a role for accumulation of mutated alleles in the process of transformation to MF. However, neither the allele burden nor the type of driver mutation influenced overall survival (OS), while absence of any driver mutation (triple negativity) was associated with significant reduction of OS in PET-MF, similar to PMF. Of the five interrogated subclonal mutations (ASXL1, EZH2, SRSF2, IDH1, and IDH2), that comprise a prognostically detrimental high molecular risk (HMR) category in PMF, only SRSF2 mutations were associated with reduced survival in PET-MF, and no additional mutation profile with prognostic relevance was highlighted. Overall, these data indicate that the molecular landscape of secondary forms of MF is different from PMF, suggesting that unknown mutational events might contribute to the progression from chronic phase disease to myelofibrosis. These findings also support more extended genotyping approaches aimed at identifying novel molecular abnormalities with prognostic relevance for patients with PPV-MF and PET-MF. Am. J. Hematol. 91:681–686, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc

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and more likely to result in viral suppression compared with lamivudine. 8 Retrospective studies have shown that tenofovir may be more effective than entecavir in patients with positive hepatitis B e-antigen, but this was not tested in the 2 patients included in this series. 9 As B-cell aplasia can be prolonged and there are no data at this time on T-cell immune reconstitution after anti-CD19 CAR T-cell therapy, antiviral prophylaxis may need to be continued long-term, as suggested by HBV reactivation experienced by the patient who self-discontinued entecavir 1 year after therapy.The small sample size does not allow us to determine any association between concomitant HBV or HCV infection and CRS or CRES. Although the etiology of these entities remains to be fully clarified, both seem to be cytokine-driven, with interleukin 6 (IL-6) representing a key molecule. 10 Patients with chronic HBV or HCV infection have higher IL-6 production than healthy controls and all 3 patients discussed herein were treated with anti-IL-6 therapy for CRS/CRES. 11 Future studies will help to clarify the impact of chronic HBV/HCV infection on the risk of CRS and CRES.

To evaluate the acute effect of human erythropoietin (r-HuEPO) on basal and stimulated prolactin (PRL) secretion, 18 normal subjects (12 females, 6 males) were studied. The PRL response to thyrothropin-releasing hormone (TRH; 200 μg intravenously, n = 7), metoclopramide (MCP, 20 mg intravenously, n = 5) and fenfluramine (FF, 60 mg os, n = 6) was tested in presence of saline or r-HuEPO (30 U/kg intravenously). The drug neither modified basal PRL levels nor affected the normal PRL release to TRH, MCP and FF. Our results indicate that, in normal subjects, the acute administration of therapeutic doses of r-HuEPO does not interfere with PRL secretion both after a direct pituitary stimulus and after stimuli involving dopaminergic and serotoninergic pathways.