Salvage therapy with pegylated liposomal doxorubicin, bortezomib, cyclophosphamide, and dexamethasone in relapsed/refractory myeloma patients.

OBJECTIVES: In vitro studies have shown synergistic anti-myeloma effects of bortezomib combined with alkylating agents or anthracycline. We tested safety and efficacy of the combination of bortezomib, doxorubicin cyclophosphamide, and dexamethasone (ABCD) in the treatment of relapsed/refractory myeloma. METHODS: ABCD consisted of bortezomib given intravenous (IV) at dosage 1.3 mg/m(2) , dexamethasone 40 mg IV on days 1, 4, 8, and 15, pegylated liposomal doxorubicin (PLD) 20 mg IV on days 1 and 15, plus cyclophosphamide 100 mg/d per os for 15 d. Between January 2008 and February 2009, 24 patients received a median of four 28-d ABCD cycles (range 1-6). All patients had been already treated with a median of two previous lines of treatment (range 1-6): 38% were resistant to previous therapies and 62% were relapsed. RESULTS: Clinical response was observed in 12 patients (50%), including 29% of very good partial remissions or better. Side effects included hematological toxicity (31% any grade), grades 3-4 thrombocytopenia (9%), grades 3-4 anemia (17%). Non-hematological toxicity affected 32% of administered cycles and included gastrointestinal disturbances (54%), peripheral neuropathy (8%), and infections (8%). After a median follow-up of 21.5 months (range 2-44 months), median of progression-free survival (PFS) was 8.7 months and median overall survival was 22.5 months. Achieving at least partial response within the second cycle was associated with a better PFS (19.5 months vs. 3.5 months), P = 0.03, HR 0.35 (CI 95% 0.13-0.90). CONCLUSION: ABCD is safe and effective for relapsed/refractory MM subjects previously treated with novel agents.

SARS-CoV-2 mRNA Vaccine Breakthrough Infections in Fully Vaccinated Healthcare Personnel: A Systematic Review.

The number of people vaccinated against COVID-19 increases worldwide every day; however, it is important to study the risk of breakthrough infections in vaccinated individuals at high risk of exposure such as healthcare personnel (HCP). A systematic literature review (SLR) applying the PRISMA declaration and the PECOS format using the following entry terms was used: "Health Personnel OR Healthcare Worker OR Healthcare Provider OR Healthcare Personnel AND breakthrough OR infection after vaccine*". The research was carried out utilizing the following databases: SCOPUS, PubMed, Embase, and Web of Sciences. An overall very low incidence of post-vaccination breakthrough infections was found, ranging from 0.011 to 0.001 (per 100 individuals at risk). Our findings further support the published high effectiveness rates of mRNA vaccines in preventing SARS-CoV-2 infections among fully vaccinated HCP. Additional studies are needed to define the duration of the vaccine-induced protection among HCP.

Rare gastrointestinal lymphomas: The endoscopic investigation.

Gastrointestinal lymphomas represent up to 10% of gastrointestinal malignancies and about one third of non-Hodgkin lymphomas. The most prominent histologies are mucosa-associated lymphoid tissue lymphoma and diffuse large B-cell lymphoma. However, the gastrointestinal tract can be the site of rarer lymphoma subtypes as a primary or secondary localization. Due to their rarity and the multifaceted histology, an endoscopic classification has not been validated yet. This review aims to analyze the endoscopic presentation of rare gastrointestinal lymphomas from disease diagnosis to follow-up, according to the involved site and lymphoma subtype. Existing, new and emerging endoscopic technologies have been examined. In particular, we investigated the diagnostic, prognostic and follow-up endoscopic features of T-cell and natural killer lymphomas, lymphomatous polyposis and mantle cell lymphoma, follicular lymphoma, plasma cell related disease, gastrointestinal lymphomas in immunodeficiency and Hodgkin's lymphoma of the gastrointestinal tract. Contrarily to more frequent gastrointestinal lymphomas, data about rare lymphomas are mostly extracted from case series and case reports. Due to the data paucity, a synergism between gastroenterologists and hematologists is required in order to better manage the disease. Indeed, clinical and prognostic features are different from nodal and extranodal or the bone marrow (in case of plasma cell disease) counterpart. Therefore, the approach should be based on the knowledge of the peculiar behavior and natural history of disease.

Long-term persistence of seroprotection by hepatitis B vaccination in healthcare workers of southern Italy.

BACKGROUND: The impact of hepatitis B virus (HBV) vaccination campaigns on HBV epidemiology needs to be evaluated, in order to assess the long-term immunity offered by vaccines against HBV. OBJECTIVES: To evaluate the current status of anti-HBV vaccine coverage among healthcare workers (HCWs) in Southern Italy, and to determine the long-term persistence of antibodies to hepatitis B surface antigens (anti-HBs) in such a cohort of subjects. PATIENTS AND METHODS: A longitudinal, retrospective seroepidemiological survey was conducted among 451 HCWs, who were working at or visiting, the Occupational Health Department of a city hospital, in Catania, Italy, between January 1976 and December 2010. RESULTS: At the 30-year follow-up (mean follow-up 10.15 ± 5.96 years, range 0.74-30), 261 HCWs had detectable anti-HBs titers indicating a persistence of seroprotection of 89.4% (out of 292 anti-HBs positive results, three months after vaccination). An inadequate vaccination schedule was the strongest predictor of antibody loss during follow-up (OR = 8.37 95% CI: 5.41-12.95, P < 0.001). A Kaplan-Maier survival curve revealed that the persistence of anti-HBs 30 years after vaccination, was 92.2% for high responders, while it was only 27.3% for low responders (P = 0.001). CONCLUSIONS: A good level of seroprotection persisted in 57.9% of the subjects after 30 years. Factors related to this immunization status confirmed the importance of vaccinating HCWs early in their careers and ensuring an adequate vaccination schedule. However, with particular reference to the low rate of hepatitis B vaccine coverage among HCWs in Southern Italy, the implementation of a new educational intervention as part of an active vaccination program is needed.

Genomic analysis: toward a new approach in breast cancer management.

Breast cancer is a clinically heterogeneous and complex disease that can affect differently individuals with seemingly identical clinicopathologic parameters. This heterogeneity is strictly linked to individuals and tumors genetic variability. Currently, the development of high-throughput technologies are proving novel tools to tackle this complexity. By DNA microarray technology, genomic analysis has been used successfully for breast carcinomas stratification into molecular subgroups with relevant implications for clinical outcomes, and detection of prognostic/treatment predictive signatures. Indeed, DNA microarray has rapidly improved becoming a powerful diagnostic tool. Information derived from these assays allows clinicians to estimate the risk for distant recurrence, and predict accurately which patients are likely to benefit from adjuvant therapy. This review will describe the state-of-the-art of genomic analysis in breast cancer and introduce the clinicians to a genomic approach to cancer management, illustrating how it can help in defying a better diagnosis, prognosis and therapeutic treatment.

CXCR4 and CXCL12 immunoreactivities differentiate primary non-small-cell lung cancer with or without brain metastases.

Synchronous or metachronous brain metastases (BMs) occur in about 33% of patients affected by non-small-cell lung cancer (NSCLC). To date, no reliable biological marker is able to identify patients who will develop BMs. In the present study, using a quantitative double-labeling immunofluorescence analysis, we evaluated the expression of chemokine CXCL12 and its receptor, CXCR4, in primary NSCLC histological specimens of patients with and without BMs. The immunoreactivity of CXCL12 and CXCR4 was significantly higher in NSCLC samples of patients with BMs. We performed Receiver Operating Characteristics (ROC) analysis in order to define optimal cut-off values for CXCL12 and CXCR4 immunoreactivity that could discriminate between NSCLC patients without and with BMs. ROC curves showed a good diagnostic accuracy and adequate predictive power for both CXCL12 and CXCR4. These findings suggest a possible role for the CXCL12/CXCR4 axis in the metastatic evolution of NSCLC, and its potential use as prognostic markers and drug targets.