Most patients with Diffuse Large B-cell Lymphoma (DLBCL) are old (>65 years of age) and this population is expected to increase in the following years. A simplified geriatric assessment based on a ...careful evaluation of the fitness status and comorbidities is essential to choose the correct intensity of treatment. Fit older patients can benefit from a standard immunochemotherapy, while unfit/frail patients frequently need reduced doses or substitution of particular agents with less toxic ones. This review focuses on new therapies (e.g., polatuzumab vedotin, tafasitamab, bispecific antibodies) that have indicated promising results in relapsed/refractory patients, particularly in cases not eligible to transplant. Some of these new drugs have been tested as single agents or in combinations as first-line treatment, aiming to improve the outcome of the traditional chemotherapy. If preliminary efficacy and safety data are confirmed in future clinical trials, a chemo-free immunotherapic approach could become an alternative option to offer a curative treatment even in frail patients.
The evaluation of the shear behavior of masonry walls is a first fundamental step for the assessment of existing masonry structures in seismic zones. However, due to the complexity of modelling ...experimental behavior and the wide variety of masonry types characterizing historical structures, the definition of masonry's mechanical behavior is still a critical issue. Since the possibility to perform in situ tests is very limited and often conflicting with the needs of preservation, the characterization of shear masonry behavior is generally based on reference values of mechanical properties provided in modern structural codes for recurrent masonry categories. In the paper, a combined test procedure for the experimental characterization of masonry mechanical parameters and the assessment of the shear behavior of masonry walls is presented together with the experimental results obtained on three stone masonry walls. The procedure consists of a combination of three different in situ tests to be performed on the investigated wall. First, a single flat jack test is executed to derive the normal compressive stress acting on the wall. Then a double flat jack test is carried out to estimate the elastic modulus. Finally, the proposed shear test is performed to derive the capacity curve and to estimate the shear modulus and the shear strength. The first results obtained in the experimental campaign carried out by the authors confirm the capability of the proposed methodology to assess the masonry mechanical parameters, reducing the uncertainty affecting the definition of capacity curves of walls and consequently the evaluation of seismic vulnerability of the investigated buildings.
Patients with B-cell lymphoma are a fragile category of subjects, particularly exposed to infections and characterized by an impaired vaccination response due to the disease itself and, even more, to ...the chemotherapy regimen. For this reason, extensive knowledge of the immune response status of these subjects is of fundamental importance to obtain possible indications for a tailored immunization strategy.
We enrolled two cohorts of patients with B-cell lymphoma under rituximab treatment or 3-24 months after treatment. In all patients, we evaluated both humoral and cellular immunological memory toward SARS-CoV-2, after standard vaccination and upon one booster dose.
We observed no Spike-specific IgG production in patients (n = 25) under anti-CD20 treatment, whereas patients (n = 16) vaccinated after the completion of chemotherapy showed a higher humoral response. Evaluating SARS-CoV-2-specific T-cell response, we found that patients in both cohorts had developed robust cellular immunity after vaccination. Of the 21 patients (51%) that experienced a breakthrough SARS-CoV-2 infection, only six patients developed severe disease. Interestingly, these six patients had all been treated with rituximab plus bendamustine. Notably, we observed that Spike-specific IgG levels in patients treated with rituximab plus bendamustine were absent or lower compared with those in patients treated with rituximab plus other chemotherapy, whereas Spike-specific T-cell response was not different based on chemotherapy regiment.
Our results show that, in patients with B-cell lymphoma under rituximab therapy, anti-SARS-CoV-2 mRNA vaccination induces a weak or absent humoral response but a consistent T-cell response. In addition, chemotherapy regimens with bendamustine further reduce patients' ability to mount a Spike-specific humoral response even after a long time period from chemotherapy discontinuation. These results provide evidence that different chemotherapeutics display different immunosuppressive properties that could be taken in to account in the choice of the right drug regimen for the right patient. Moreover, they question whether immunocompromised patients, particularly those treated with bendamustine, need interventions to improve vaccine-induced immune response.
•Unimodal TRBC1 pattern correlates with T cell clonality.•A TRBC1-including multiparametric panel improves clonality assessment sensitivity.•Monitoring TRBC1 helps in identifying small T-cell clones ...of uncertain significance.•TRBC1 represents an opportunity to overcome time-consuming diagnostic strategies.
The identification of mature T cell neoplasms by flow cytometry is often challenging, due to overlapping features with reactive T cells and limitations of currently available T cell clonality assays. The description of an antibody specific for one of two mutually exclusive T cell receptor (TCR) β-chain constant regions (TRBC1) provides an opportunity to facilitate the detection of clonal TCRαβ+ T cells based on TRBC-restriction. Here we prospectively analyzed 14 healthy controls and 63 patients with the flow cytometry protocol currently used for suspected T cell neoplasm implemented with immunostaining targeting TRBC1. Specimens were firstly classified in 3 groups based on clinical records data, laboratory findings and immunophenotypic features. T cell clonality was assessed by TCR Vβ repertoire analysis and the new rapid TRBC1 assay. Results showed that TRBC1 unimodal expression was unequivocally associated with samples presenting with immunophenotypic aberrancies. Moreover, we demonstrated that the use of TRBC1 is useful in solving uncertain cases and confirmed the high sensitivity of the method in identifying small T cell clones of uncertain significance (T-CUS). Finally, we found a high degree of concordance (97%) comparing the currently available clonality assessment methods with the proposed new method. In conclusion, our results provided real-life evidence of the utility of TRBC1 introduction in the flow cytometric clonality evaluation for the routine diagnostic work-up of T cell neoplasms.
In the architecture, engineering and construction sectors, Building Information Modeling (BIM)-based procedures have become adopted more and more. In fact, the development of suitable BIM models ...facilitates the management of the design and construction phases and improves the efficiency of the maintenance policies during the life cycle of the building. Although the BIM method is mostly implemented in the building industry for new constructions, in recent years, the deployment of this technology has also attracted increasing attention for existing structures to rebuild their geometry and gather relevant data, especially for historical buildings; in this case, we refer to Heritage BIM (HBIM). A HBIM procedure requires a multidisciplinary approach involving not only historical, conservation, and restoration considerations but also suitable maintenance and repair plans, duly balancing the structural needs with the preservation of the historical value of the building and its content. Although the integration of the structural assessment in the HBIM process would be highly beneficial, its practical implementation is often in the early stages. In the paper, an original parametric procedure for the assessment of existing masonry buildings is proposed in the BIM environment. The procedure combines E-PUSH, a software program for the structural analysis of masonry structures under seismic and non-seismic actions with an appropriate BIM approach, so improving the management of gathered data through cognitive phases. The assessment process is, thus, simplified since data required for the structural analysis are directly retrieved from the BIM model, and the structural analyses and verifications are performed without using external programs. The proposed BIM workflow is finally illustrated and discussed referring to a relevant case study, the seismic vulnerability assessment of the “Bernardo Rucellai” school in Florence (Italy).
Octogenarian patients with diffuse large B-cell lymphoma are managed mainly with palliation, but recent improvement in their overall condition makes potentially curative treatment a possibility. ...Studies have shown that half of selected octogenarians may be cured using reduced-dose anthracycline chemoimmunotherapy. However, patients aged >85 (late octogenarians LO) were underrepresented, and selection criteria were poorly defined. We analyzed the clinical characteristics and outcomes of LO enrolled in the FIL Elderly Project in terms of the treatment received (palliative vs. curative) and of their simplified geriatric assessment (sGA), then compared them with early octogenarians (EO) aged 80- 84 and with those aged 65-79 classified as UNFIT or FRAIL according to sGA enrolled in the same study. Of the 1,163 patients, 370 were >80 and 129 LO. Clinical characteristics were similar between LO and EO, but LO more frequently received palliation (50% vs. 23%; P=0.001) and had worse 2-year overall survival (OS) (48% vs. 63%; P=0.001) and 2-year progression-free survival (PFS) (43% vs. 56%; P=0.01). Patients receiving anthracycline did better than patients receiving palliation (P<0.001), without any difference between full or reduced doses. Rituximab within palliation improved outcome (2-yr OS with or without rituximab 42% vs. 22%; P=0.008). Elderly Prognostic Index (EPI) performed better than sGA in identifying different risk categories, and high-risk EPI retained an independent unfavorable effect on OS and PFS, together with treatment without anthracycline. In conclusion, late octogenarians can benefit from a curative approach with reduced-dose anthracycline and from rituximab within palliation. EPI may help in patient selection more than sGA can.
This study tested the diagnostic value of 18F-FDG PET/CT (FDG-PET) volumetric and texture parameters in the histological differentiation of mediastinal bulky disease due to classical Hodgkin lymphoma ...(cHL), primary mediastinal B-cell lymphoma (PMBCL) and grey zone lymphoma (GZL), using machine learning techniques.
We reviewed 80 cHL, 29 PMBCL and 8 GZL adult patients with mediastinal bulky disease and histopathological diagnoses who underwent FDG-PET pre-treatment. Volumetric and radiomic parameters were measured using FDG-PET both for bulky lesions (BL) and for all lesions (AL) using LIFEx software (threshold SUV ≥ 2.5). Binary and multiclass classifications were performed with various machine learning techniques fed by a relevant subset of radiomic features.
The analysis showed significant differences between the lymphoma groups in terms of SUVmax, SUVmean, MTV, TLG and several textural features of both first- and second-order grey level. Among machine learning classifiers, the tree-based ensembles achieved the best performance both for binary and multiclass classifications in histological differentiation.
Our results support the value of metabolic heterogeneity as an imaging biomarker, and the use of radiomic features for early characterization of mediastinal bulky lymphoma.
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