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Abstract: Stromboli, one of the very few tourist volcanic islands in the world in permanent state of activity, has been the site of two important volcanic crises coupled with slope failure episodes in 2002–2003 and 2007. Due to the lucky circumstance that both crises have occurred in winter, the actual consequences on people were moderate. Nevertheless, the first crisis caused a few injuries, threatened the local population and caused relevant economic losses. The emotional impact on public opinion of the 30th December 2002 tsunami acted, in particular, as a trigger for civil protection initiatives aimed at structurally improving the standard volcano safety and preparedness measures to effectively deal with future crises. The main initiatives carried out during the 2003 crisis consisted in the setting up of: 1) new geophysical and geochemical volcano surveillance networks and 2) a local, permanent scientific/civil protection structure (COA, Centro Operativo Avanzato), where signals from volcano monitoring are visualized in real time and eventually used by the personnel of the Department of Civil Protection (DPC) for immediate activation of response procedures. This was followed by the setting up, in 2005, at the (DPC) in Rome, of a centre named “Centro Funzionale Centrale Rischio Vulcanico” (CFCRV), where the most relevant monitoring signals of Italian active volcanoes are visualized in real time and where activities of simple elaboration, for hazard assessment purpose are daily carried out and data sharing within the scientific community is coordinated by civil protection personnel with training in volcanic problems. The response effectiveness of the new system was tested on February–March 2007 when a new volcanic crisis occurred. An internal DPC “state of attention” was declared by the CF 15 days before the eruption onset when seismic and deformation parameters showed an abrupt increase up to values much higher than background. On February 27th the sudden onset of explosive activity outside the main craters and the occurrence of a small landslide down slope of the active craters were detected in real time on the screens of the CFCRV and by monitoring centres of the National Institute of Geophysics and Volcanology (INGV) and University of Florence (UNIFI). This enabled the DPC to immediately activate emergency crisis procedures and start a coordinated management of the crisis between civil protection personnel in Rome and COA. As accelerating slope movements were detected by ground deformation monitoring of UNIFI, a tsunami warning was launched shortly afterward. Warnings were also declared on 8th March and 15th March when slope movements resumed and a large explosion at the central craters occurred, respectively. From the end of February to May 2007 a scientific committee named “Scientific Synthesis Group” (SSG), appointed by the DPC, made daily evaluations of impending hazards in cooperation with CFCRV. During the crisis the DPC coordinated information activities with the media and island residents. The successful managing of the crisis consisted in minimizing risk for people and meanwhile facilitating normal activities and regular access to island. [Copyright &y& Elsevier]

We performed an observational study on the efficacy of ben-damustine and rituximab (BR) as first salvage regimen in chronic lymphocytic leukemia (CLL). In an intention-to-treat analysis including 237 patients, the median progression-free survival (PFS) was 25 months. The presence of del(17p), unmutated IGHV and advanced stage were associated with a shorter PFS at multivariate analysis. The median time-to-next treatment was 31.3 months. Front-line treatment with a chemoimmunotherapy regimen was the only predictive factor for a shorter time to next treatment at multivariate analysis. The median overall survival (OS) was 74.5 months. Advanced disease stage (i.e. Rai stage III-IV or Binet stage C) and resistant disease were the only parameters significantly associated with a shorter OS. Grade 3-5 infections were recorded in 6.3% of patients. A matched-adjusted indirect comparison with ibrutinib given second-line within Named Patient Programs in the United Kingdom and in Italy was carried out with OS as objective end point. When restricting the analysis to patients with intact 17p who had received chemoimmunotherapy in first line, there was no difference in OS between patients treated with ibrutinib (63% alive at 36 months) and patients treated with BR (74.4% alive at 36 months). BR is an efficacious first salvage regimen in CLL in a real-life population, including the elderly and unfit patients. BR and ibrutinib may be equally effective in terms of OS when used as first salvage treatment in patients without 17p deletion., (Copyright© 2018 Ferrata Storti Foundation.)

The front-line therapy for CLL young and fit patients is chemo-immunotherapy with fludarabine-cyclophosphamide-rituximab (FCR). FCR regimen results in a significant myelosuppression and high rates of early and late infections especially in elderly patients. German CLL study group compared FCR vs. bendamustine-rituximab (BR) in fit untreated patients. The response rates with BR or FCR were comparable, BR could be an alternative 1st-line treatment for elderly patients. Here we report retrospective data of 70 elderly (≥65 years) CLL patients from 12 Italian centers treated with BR as front-line therapy. The primary end points were overall response rate (complete remission/partial remission) and safety. Forty-seven males and 23 females, with a median age of 72 years, were included in the study. Eight patients were unfit for CIRS. The OR rate was 88.6% (31.4% CR and 57.2% PR). Progression free survival, treatment free survival and overall survival rates at 2-years were 79%, 90.3% and 89.6%, respectively. Only del17 was independent unfavorable parameter on the response rate and PFS. Our results indicate that BR front-line at standard dose provides a high response rate with a good safety profile, even if more than 50% of patients experienced a bendamustine dose reduction until 70 mg/m2., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Although the coexistence of chronic lymphocytic leukemia (CLL) and myeloproliferative neoplasms (MPN) has been sporadically reported in the literature, no systematic studies on this disease association are available. We retrospectively analyzed 46 patients affected by CLL/MPN referred by 15 Italian GIMEMA centers. The aim of this retrospective multicenter study was to define the following: clinico-biological characteristics, possible familiarity, clinical course of both diseases, and influence of MPN chemotherapy on the course of CLL. Among 46 patients, 30 patients were males, 16 patients were females; median age was 71 years. Only one case had familiar CLL. Myeloproliferative disorders consisted of essential thrombocytemia in 18 cases, polycythemia vera in 10 cases, chronic myeloid leukemia in 9 cases, primary myelofibrosis in 6 cases, and MPN/myelodysplastic syndrome in 3 cases. The lymphoproliferative disorder was diagnosed as monoclonal B-cell lymphocytosis in 8 patients and as Binet Stage A CLL in 38 patients. After a median follow-up of 49 months, 9 patients experienced progressive CLL and only 6 patients required treatment after a median of 57.5 months. The biological profile confirmed a subset of low-risk CLL. Twenty patients received chemotherapy for MPN without influence on the course of CLL: lymphocyte counts remained unchanged after 3, 6, and 12 months of treatment. This series is the largest so far reported in literature. The diagnosis of concomitant CLL/MPN is a rare event and lymphoproliferative disorders present a clinical indolent course with a low-risk biological profile. MPN therapy does not interfere with the prognosis of patients with CLL., (Copyright © 2011 Wiley-Liss, Inc.)

Renal impairment (RI) is a severe complication throughout the course of multiple myeloma (MM). Bortezomib has been shown to be highly active in MM patients with RI. We designed this retrospective analysis to investigate the safety and efficacy of bortezomib-based therapy in 117 MM patients with RI, 14 cases required dialysis. A total of 603 cycles of bortezomib were administered (median number, five cycles/patient). Ten patients required early discontinuation of bortezomib because of WHO grade IV toxicity. The rate of bortezomib discontinuation in cases with severe, moderate and mild RI was 11%, 5% and 0%, respectively (P = NS). Overall, 91 episodes of WHO grade III/IV toxicity were observed. At least a partial response was documented in 83/113 evaluable patients (73%), including complete response (19%) and near complete response (8%). The overall response rate was similar across RI subgroups. Reversal of RI was documented in 41% of patients after a median of 2.3 months (range 0.4-7.9). In three of 14 patients on dialysis, renal replacement therapy was discontinued after 1, 1 and 4 months. The 2-yr estimate of response duration and overall survival was 70% and 51%, respectively. In conclusion, bortezomib-based regimens are safe and effective and should be considered as appropriate treatment options for MM patients with any degree of RI.