Survival prediction in essential thrombocythaemia (ET) and polycythaemia vera (PV) is currently based on clinically-derived variables; we examined the possibility of integrating genetic information for predicting survival. To this end, 906 molecularly-annotated patients (416 Mayo Clinic; 490 University of Florence, Italy), including 502 ET and 404 PV, were recruited. Multivariable analysis identified spliceosome mutations to adversely affect overall (SF3B1, SRSF2 in ET and SRSF2 in PV) and myelofibrosis-free (U2AF1, SF3B1 in ET) survival; TP53 mutations predicted leukaemic transformation in ET; "adverse" mutations occurred in 51 (10%) ET and 8 (2%) PV patients. We confirmed the independent survival effect of adverse mutations [hazard ratio (HR) 2Á4, 95% CI 1Á6-3Á5], age >60 years (6Á6, 4Á6-9Á7), male sex (1Á8, 1Á3-2Á4) and leukocytosis ≥11 9 10 9 /l (1Á6, 1Á1-2Á2), in ET, and adverse mutations (7Á8, 3Á1-17Á0), age >67 years (5Á4, 3Á6-8Á1), leukocytosis ≥15 9 10 9 /l (2Á8, 1Á8-4Á2) and thrombosis history (2Á0, 1Á4-2Á9), in PV. HR-based risk point allocation allowed development of three-tiered mutation-enhanced international prognostic systems (MIPSS) which were validated in both cohorts and performance was shown to be superior to conventional scoring systems. Spliceosome mutations enhance survival prediction in ET and PV and identify patients at risk for fibrotic progression. TP53 mutations predict leukaemic transformation in ET.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/ JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus highflow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Myeloproliferative Neoplasms (MPN) course can be complicated by thrombosis involving unusual sites as the splanchnic veins (SVT). Their management is challenging, given

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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.

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