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Despite effective treatments, cytomegalovirus (CMV) continues to have a significant impact on morbidity and mortality in allogeneic stem cell transplant (allo-SCT) recipients. This multicenter, retrospective, cohort study aimed to evaluate the reproducibility of the safety and efficacy of commercially available letermovir for CMV prophylaxis in a real-world setting. Endpoints were rates of clinically significant CMV infection (CSCI), defined as CMV disease or CMV viremia reactivation within day +100-+168. 204 adult CMV-seropositive allo-SCT recipients from 17 Italian centres (median age 52 years) were treated with LET 240 mg/day between day 0 and day +28. Overall, 28.9% of patients underwent a haploidentical, 32.4% a matched related, and 27.5% a matched unrelated donor (MUD) transplant. 65.7% were considered at high risk of CSCI and 65.2% had a CMV seropositive donor. Low to mild severe adverse events were observed in 40.7% of patients during treatment [gastrointestinal toxicity (36.3%) and skin rash (10.3%)]. Cumulative incidence of CSCI at day +100 and day +168 was 5.4% and 18.1%, respectively, whereas the Kaplan-Meier event rate was 5.8% (95% CI: 2.4-9.1) and 23.3% (95% CI: 16.3-29.7), respectively. Overall mortality was 6.4% at day +100 and 7.3% at day +168. This real-world experience confirms the efficacy and safety of CMV.

Breast cancer is one of the most frequently diagnosed forms of cancer and different treatments are used to block its progression. However, it still represents a very common cause of death in women. Doxorubicin (Dox) is reported as an effective agent in breast cancer treatment nonetheless it induces many side‑effects. For this reason, many laboratories are engaged in understanding how it is possible to decrease the drug concentration, considering that one of the possible solutions is to use drug synergy, combining it with natural substances. Recently we showed that a phenolic extract from flaxseed (FS) oil, named PEFSO, induced on MCF‑7 cell line an increase of apoptosis with related modification of G0/G1 phase cell cycle, and the activation of signaling and pro‑oxidant pathways. In this study we present data on the combined effect of Dox and PEFSO on two different breast cancer cell lines to define the conditions to use lower doses of this chemotherapeutic agent. We report the data relating to the ability of this mixture to induce cytotoxicity and apoptosis, cell cycle modification, mitochondrial membrane depolarization and activation of extrinsic and/or intrinsic apoptotic pathway.

Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506) has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B) were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i) a strong cell apoptosis induction, (ii) contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii) downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

Background. HCMV is the most opportunistic viral agent in the transplantation of bone marrow and solid organ. Early therapy based on the detection of HCMV pp65 antigen in peripheral blood leukocytes, has led to a significant reduction in the incidence of related HCMV diseases.The pp65 antigenemia is difficult to standardize, while the quantification of HCMV DNA by Real-Time PCR is an alternative diagnostic approach with greater sensitivity and reproducibility, providing important information in the management of infected patients. Objectives. The aim of this study was the comparative analysis of quantitative HCMV DNAemia in leukocytes and in whole blood, with Real-time PCR, in a BMT patient with HCMV post-transplant reactivation, in order to analyze the relationship between levels of viral DNA at different time-points obtained in the two biological matrices. Study Design. The presence of HCMV DNA was detected in whole blood and peripheral blood leukocytes in a patient who underwent allogeneic marrow transplant for Ph1 + acute lymphoblastic leukemia in molecular remission. After 5-6 months, the patient has increased molecular Bcr-Abl (Philadelphia chromosome). It was activated immune reaction by means of tapering (lowering the dose of cyclosporine) that uses the GvL effect to turn negative the Philadelphia chromosome positivity (Bcr/Abl negativity). Later, the patient develops GvHD and cortisone is administered. The persistence of grafts treated with immunosuppressants periodically reactivates HCMV infection. The DNA extraction from whole-blood was performed by automatic extractor QIACUBE (Qiagen), while extraction from leucocytes was performed on a standard number of leukocytes (EXTRAcell- Nanogen).The extracted DNA was amplified by Real-Time Alert Q-PCR (Nanogen).The samples were analyzed weekly for about 5 months from 1 year after transplantation. Results. The patient at 1 year after transplantation, has three HCMV reactivation at 56th, 62th and 67th week. In all reactivations a good overlap values of viraemia in both whole blood leukocytes is shown. Conclusions. Our data confirm that the whole blood is a biological matrix with diagnostic similar performance not only to pp65 antigenaemia, as supported by extensive scientific literature, but also to the DNAemia in leukocytes that has been for a long time considered the elective matrix for evaluating the post-transplant HCMV infection, for pre-emptive therapy particularly in BMT patients.