Daratumumab-based regimens for patients with multiple myeloma plus extramedullary plasmacytomas or paraskeletal plasmacytomas: initial follow-up of an Italian multicenter observational clinical experience.

Myeloma with extramedullary plasmacytomas not adjacent to bone (EMP) is associated with an extremely poor outcome compared with paraosseous plasmacytomas (PP) as current therapeutic approaches are unsatisfactory. The role of new molecules and in particular of monoclonal antibodies is under investigation. To determine whether daratumumab-based regimens are effective for myeloma with EMP, we report herein an initial multicenter observational analysis of 102 myeloma patients with EMP (n = 10) and PP (n = 25) at diagnosis and EMP (n = 28) and PP (n = 39) at relapse, treated with daratumumab-based regimens at 11 Haematological Centers in Italy.EMP and PP at diagnosis were associated with higher biochemical (90% vs. 96%, respectively) and instrumental ORR (86% vs. 83.3%, respectively), while at relapse, biochemical (74% vs. 73%) and instrumental (53% vs. 59%) ORR were lower. Median OS was inferior in EMP patients compared with patients with PP both at diagnosis (21.0 months vs. NR) (p = 0.005) and at relapse (32.0 vs. 40.0 months) (p = 0.428), although, during relapse, there was no statistically significant difference between the two groups. Surprisingly, at diagnosis, median TTP and median TTNT were not reached either in EMP patients or PP patients and during relapse there were no statistically significant differences in terms of median TTP (20 months for two groups), and median TTNT (24 months for PP patients vs. 22 months for EMP patients) between the two groups. Median TTR was 1 month in all populations.These promising results were documented even in the absence of local radiotherapy and in transplant-ineligible patients.

High Ki67 index and bulky disease remain significant adverse prognostic factors in patients with diffuse large B cell lymphoma before and after the introduction of rituximab.

The aim of this study was to evaluate the impact of clinical variables and biologic features on response rate (RR), overall survival (OS) and progression-free survival (PFS) in 111 patients with de novo diffuse large B cell lymphoma (DLBCL). Fifty-three patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and 58 patients were treated with R-CHOP (rituximab + CHOP). The variables predictive of RR in the CHOP group were B symptoms, age, clinical stage, bone marrow involvement, bulky disease, International Prognostic Index (IPI) and Bcl-2; in the R-CHOP group, these variables were bulky disease, bone marrow involvement, IPI and Ki67 expression >80%. Multivariate analysis showed that in patients treated with CHOP, the independent prognostic factors associated with PFS were age, bulky disease, IPI and Bcl-2 and those associated with OS were performance status, clinical stage, IPI and bone marrow involvement. In contrast, in patients treated with R-CHOP, the variable shown by multivariate analysis to be an independent prognostic factor associated with PFS was bulky disease, whereas Ki67 expression >80% was associated with OS and PFS. Our data show that a high Ki67 expression and bulky disease could represent possible predictive factors of poor prognosis, which would help to identify a high-risk subgroup of newly diagnosed DLBCL.

Intense overpressurization at basaltic open-conduit volcanoes as inferred by geochemical signals: The case of the Mt. Etna December 2018 eruption.

The balance between the amount of gas coexisting with mantle-derived magmas at depth and that emitted during intereruptive phases may play a key role in the eruptive potential of volcanoes. Taking the December 2018 eruption at Mt. Etna volcano as a case study, we discuss the geochemical data streams observed. The signals indicate a long-lasting prelude stage to eruption, starting in 2017 and involving magma-fluid accumulation in the deep (>7 km bsl) reservoir, followed by pressure buildup in the system at intermediate depth (5 to 2 km bsl), 6 to 7 months before the eruption. A brief preeruptive phase marks the pressurization at 2 to 3 km below the craters. By comparing the magma and fluid recharge at depth to the measured volcanic degassing from the plume, we provide evidence that Mt. Etna was in a state of extreme overpressurization in the weeks before the onset of the eruption.

Small-scale volcanic aerosols variability, processes and direct radiative impact at Mount Etna during the EPL-RADIO campaigns.

The aerosol properties of Mount Etna's passive degassing plume and its short-term processes and radiative impact were studied in detail during the EPL-RADIO campaigns (summer 2016-2017), using a synergistic combination of observations and radiative transfer modelling. Summit observations show extremely high particulate matter concentrations. Using portable photometers, the first mapping of small-scale (within [Formula: see text] from the degassing craters) spatial variability of the average size and coarse-to-fine burden proportion of volcanic aerosols is obtained. A substantial variability of the plume properties is found at these spatial scales, revealing that processes (e.g. new particle formation and/or coarse aerosols sedimentation) are at play, which are not represented with current regional scale modelling and satellite observations. Statistically significant progressively smaller particles and decreasing coarse-to-fine particles burden proportion are found along plume dispersion. Vertical structures of typical passive degassing plumes are also obtained using observations from a fixed LiDAR station constrained with quasi-simultaneous photometric observations. These observations are used as input to radiative transfer calculations, to obtain the shortwave top of the atmosphere (TOA) and surface radiative effect of the plume. For a plume with an ultraviolet aerosol optical depth of 0.12-0.14, daily average radiative forcings of [Formula: see text] and [Formula: see text], at TOA and surface, are found at a fixed location [Formula: see text] downwind the degassing craters. This is the first available estimation in the literature of the local radiative impact of a passive degassing volcanic plume.

Response to pomalidomide plus fixed low-dose dexamethasone in a case of secondary plasma cell leukaemia.

This is, to our knowledge, the first reported case of secondary Plasma Cell Leukemia that was successfully by pomalidomide plus fixed low-dose dexamethasone. Pomalidomide at a dosage of 4 mg orally on days 1-21 of repeated 28-day cycles associated with fixed low-dose dexamethasone (40 mg on days 1, 8, 15 and 22 of each 28-day cycle), outside of the clinical trials, was started as a final attempt. After the fourth course, the patient achieved an interesting response that included a significant reduction of circulating plasma cells from the peripheral blood, a very important decrease of the M-component, and normalization of haematological value. The toxicities were acceptable. The time to best response was 4 months.

Outcome of Very Late Relapse in Patients with Hodgkin's Lymphomas.

Recurrences of Hodgkin's Lymphoma (HL) 5 years after the initial therapy are rare. The aim of this study is to report a single centre experience of the clinical characteristics, outcome, and toxicity of pts who experienced very late relapses, defined as relapses that occurred 5 or more years after the achievement of first complete remission. Of 532 consecutive pts with classical HL treated at our Institute from 1985 to 1999, 452 pts (85%) achieved a complete remission. Relapse occurred in 151 pts: 135 (29.8%) within 5 years and 16 over 5 years (3.5%, very late relapses). Very late relapses occurred after a median disease-free interval of 7 years (range: 5-18). Salvage treatment induced complete remission in 14 pts (87.5%). At a median of 4 years after therapy for very late relapse, 10 pts (63%) are still alive and free of disease and 6 (37%) died (1 from progressive HL, 1 from cardiac disease, 1 from thromboembolic disease, 1 from HCV reactivation, and 2 from bacterial infection). The probability of failure-free survival at 5 years was 75%. The majority of deaths are due to treatment-related complications. Therapy regimens for very late relapse HL are warranted to minimize complications.

Magmatic gas composition reveals the source depth of slug-driven strombolian explosive activity.

Strombolian-type eruptive activity, common at many volcanoes, consists of regular explosions driven by the bursting of gas slugs that rise faster than surrounding magma. Explosion quakes associated with this activity are usually localized at shallow depth; however, where and how slugs actually form remain poorly constrained. We used spectroscopic measurements performed during both quiescent degassing and explosions on Stromboli volcano (Italy) to demonstrate that gas slugs originate from as deep as the volcano-crust interface (approximately 3 kilometers), where both structural discontinuities and differential bubble-rise speed can promote slug coalescence. The observed decoupling between deep slug genesis and shallow (approximately 250-meter) explosion quakes may be a common feature of strombolian activity, determined by the geometry of plumbing systems.