Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, which targets different osteoblast (OBs) differentiation markers, is enriched in MM-EVs compared to SMM-EVs, thus suggesting a selective packaging correlated with pathological grade. We found that miR-129-5p can be transported to hMSCs by MM-EVs and, by the use of miRNA mimics, we investigated its role in recipient cells. Our data demonstrated that the increase of miR-129-5p levels in hMSCs under osteoblastic differentiation stimuli inhibited the expression of the transcription factor Sp1, previously described as a positive modulator of osteoblastic differentiation, and of its target the Alkaline phosphatase (ALPL), thus identifying miR-129-5p among the players of vesicle-mediated bone disease.

One of the most important determinants of aging-related changes is a complex biological process emerged recently and called “immunosenescence”. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way.This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of two main lymphoma groups, namely Non Hodgkin Lymphoma (NHL) and Hodgkin Lymphoma (HL). Epstein Barr Virus (EBV) plays a central role in the onset of neoplastic lymphoproliferation associated with immunological changes in aging, although the pathophysiology varies vastly among different disease entities. The interaction between immune dysfunction, immunosenescence and Epstein Barr Virus (EBV) infection appears to differ between NHL and HL, as well as between NHL subtypes.

Background: The ASPIRE (NCT01080391) phase 3 trial showed the efficacy of carfilzomib, lenalidomide and dexamethasone (KRd) triplet for relapse and refractory multiple myeloma (RRMM). However, little is known about safety and efficacy of KRd outside a clinical trial context. Methods: Herein we report real life results of KRd given to 130 RRMM patients from 12 Sicilian Centers. Results: Median age was 62 years; patients had received a median of two previous lines of treatment (range 1–10) and 52% were refractory to previous treatment. Median number of KRd cycles was 12 (2–29), with a mean duration of treatment of 12 months; 21 patients had received at least 18 cycles. Overall response rate was 61%, including 18% complete response. Median PFS was 22.9 months, median OS was not reached. Creatinine clearance >30 mL/min, quality of the best achieved response and standard Fluorescence In Situ Hybridization (FISH) risk were independent predictors of favorable outcome. Patients who received the full-dosage of carfilzomib in the first two cycles had a better outcome. Conclusions: KRd was effective and well tolerated and in a considerable proportion of patients, therapy continued beyond the 18th cycle. The finding of a better outcome in patients with the higher cumulative dose of carfilzomib in the first two cycle encourages to maintain the maximum tolerated dose.

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has undergone several revisions. Recently, the revised-IPSET-t has distinguished 4 risk classes, from very low risk to high risk. Driver mutations seem to influence thrombotic risk and prognosis, while the role of sub-driver mutations still remains uncertain. Antiplatelet therapy is recommended in all patients aged ⩾ 60 years and in those with a positive history of thrombosis or with cardiovascular risk factors, while cytoreductive therapy with hydroxyurea or interferon is reserved for high-risk patients.

The thyroid gland is often involved in the development of neoplastic diseases, including lymphoproliferative disorders. The aim of this paper is to provide a comprehensive overview of the multiple interactions between lymphoma and thyroid. Through an extensive research among the literature, the relationship between lymphomas and thyroid can be established at various levels, and the possible interconnections are here summarized in 5 points: (1) the greater risk of lymphoma development in some thyroid diseases; (2) the primary thyroid lymphoma, with focus on issues related to the diagnosis, differential diagnosis, and treatment; (3) the incidence of thyroid involvement in primitive nodal lymphomas or in extranodal lymphomas of the other sites; (4) thyroid changes after treatment of lymphoma, in relation to the effects of radiation therapy and immuno-chemotherapy; (5) the incidental findings of thyroid changes, on imaging, in patients with lymphoma, without a direct involvement of the gland in malignant disease. In conclusion, issues that until now have been dealt with separately will therefore be analyzed in a unique paper, allowing a global view of the topic and emphasizing the need of a multidisciplinary approach. Future learning areas in this topic mainly relate to rapidly increasing the knowledge of imaging studies together with expanding the armamentarium of novel biological and targeting agents in lymphoma patients.