Controls on explosive-effusive volcanic eruption styles

One of the biggest challenges in volcanic hazard assessment is to understand how and why eruptive style changes within the same eruptive period or even from one eruption to the next at a given volcano. This review evaluates the competing processes that lead to explosive and effusive eruptions of silicic magmas. Eruptive style depends on a set of feedbacks involving interrelated magmatic properties and processes. Foremost of these are magma viscosity, gas loss, and external properties such as conduit geometry. Ultimately, these parameters control the speed at which magmas ascend, decompress and outgas en route to the surface, and thus determine eruptive style and evolution

Outcome in patients with diffuse large B-cell lymphoma who relapse after autologous stem cell transplantation and receive active therapy. A retrospective analysis of the Lymphoma Working Party of the European Society for Blood and Marrow Transplantation (EBMT)

Autologous hematopoietic stem cell transplantation (auto-HSCT) is the standard of care for patients with diffuse large B-cell lymphoma (DLBCL) who relapse/progress after first line chemoimmunotherapy. Long-term outcome of those who relapse after transplant is poor. We present the results of a retrospective study of 256 adult patients reported to the EBMT registry with DLBCL who relapsed after auto-HSCT performed between 2003 and 2013, and who received active salvage strategies. One hundred and fifty-four (60%) were male; median age was 53 years. Median time to relapse was 7 months, 65% relapsed during the first year. Overall response rate after salvage therapy was 46%. Median follow-up after first salvage therapy was 40 months (IQR 23–63 months). Overall survival (OS) at 3 years was 27% (95% CI 22–33). OS at 3 years of patients relapsing longer than 1 year after auto-HSCT was 41% (95% CI 31–53) compared with 20% (95% CI 14–24) in those who relapsed in less than 1 year. Eighty-two patients (32%) had a second HSCT, an allogeneic HSCT (allo-HSCT) in 69 cases, at a median time of 6.5 months after relapse. OS at 3 years after allo-HSCT was 36% (95% CI 25–51). In conclusion, the prognosis of patients with DLBCL that relapse after auto-HSCT is dismal. Patients who relapse in less than 1 year remain an unmet need, and should be considered for CAR T cell therapy or clinical trials. Patients who relapse after 1 year can be rescued with salvage therapies and a second HSCT. These results provide a benchmark to compare data of new prospective studies

HIGH DOSE SEQUENTIALCHEMOTHERAPY WITH RITUXIMAB AND ASCT AS FIRST LINE THERAPY IN ADULT MCL PATIENTS: CLINICAL AND MOLECULARRESPONSE OF THE MCL0208 TRIAL, A FIL STUDY

Background: In spite of the improvement of the disease control obtained with the intensive chemo-immunotherapy in adult patients with MCL with or without autograft (ASCT) the rate of relapse and death is still high. Recent data showed that a therapeutic strategy including a maintenance in responding patients to chemoimmunotherapy can prolong the response duration and clinical outcome of MCL patients. Aims: In 2008 the Fondazione Italiana Linfomi (FIL) designed the phase III trial MCL0208, to evaluate the efficacy and safety of lenalidomide as maintenance therapy in patients with MCL achieving at least a Partial Response (PR) after an upfront intensive chemotherapy with rituximab (R) and ASCT (NCT02354313). This trial was approved by the Ethical Committee of all partecipating centers. Herein, we present the analysis of clinical and molecular response after the chemotherapy with Rituximab (R) and ASCT, one of the secondary objectives of MCL0208 study. Methods: Adult patients aged5 cm) (33%), elevated LDH (31%), BM infiltration (76%) and intermediate-high MIPI (53%). Nine percent of patients had blastoid variant. Among the 260 enrolled patients, 187 completed R-HDS (72%). Ultimately, 168 patients (65%) proceed to ASCT and 146 (56%) have been randomized between lenalidomide or observation. At the time of the present analysis according to Cheson (JCO 2007) of 202 patients evaluable for final response 137 (68%) reached CR after RHDS and 156 (77%) after ASCT. Regarding MRD a molecular marker was found in 87% of cases. Before ASCT a complete molecular response (CMR) on PB and BM were 72% and 53% by nested PCR and 80% and 67% by RQ-PCR. After ASCT CMR on PB and BM were 79% and 50% by nested PCR and 86% and 73% by RQ-PCR. After a median fol- low-up of 19 months the 2-year PFS and OS were 77% and 88%, respectively. As expected with intensive regimens there was an hematological toxicity, particularly CTC grade 3-4 neutropenia (38% of cycles) and thrombocytopenia (31% of cycles), but the infections were recorded only in 17% of patients and the treatment-related deaths (TRD) were 1.6%. Summary and Conclusions: RHDS with ASCT is a feasible regimen with limited toxicity in a multicenter setting and produces an high rate of durable responses. These promising results are supported by the high rate of molecular responses by RQ-PCR

Met signaling regulates growth, repopulating potential and basal cell-fate commitment of mammary luminal progenitors: implications for basal-like breast cancer

Basal-like breast cancer is an aggressive subtype of mammary carcinoma. Despite expressing basal markers, typical of mammary stem cells, this tumor has been proposed to originate from luminal progenitors, which are downstream of stem cells along the mammary epithelial hierarchy. This suggests that committed luminal progenitors may reacquire basal, stem-like characteristics, but the mechanisms that regulate this transition remain unclear. Using mouse models, we found that luminal progenitors express high levels of the Met receptor for hepatocyte growth factor (HGF), as compared with the other mammary epithelial sub-populations. Constitutive activation of Met led luminal progenitors to attain stem cell properties, including enhanced clonogenic activity in vitro and de novo ability to reconstitute mammary glands in repopulation assays in vivo. Moreover, in response to Met signaling, luminal progenitors gave rise to hyperplastic ductal morphogenesis and preferentially underwent basal lineage commitment at the expense of luminal cell-fate specification. Opposite and symmetric results were produced by systemic pharmacological inhibition of Met. Hence, Met signaling targets luminal progenitors for expansion, impairs their differentiation toward the mature luminal phenotype and enables their commitment toward the basal lineage. These results emphasize a critical role for Met in promoting deregulated proliferation and basal plasticity of normal luminal progenitors in the mammary gland, a complex of events that may be required for sustaining the functional and phenotypic properties of basal-like breast tumors