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B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.

The albumin/fibrinogen ratio is a cheap, simple, useful and independent biological marker used in several clinical disorders. Particularly, it has been evaluated in different types of malignant neoplasms and in this regard, in recent years, many researchers have focused this topic. In this paper, we examined the behaviour of this parameter in a cohort of newly diagnosed multiple myeloma patients. The study population includes 190 patients (mean age of 69+/- 10 years of which 88 were women and 102 were men) in which the albumin/fibrinogen ratio was determined at the time of diagnosis and the study enrolment. We have examined this ratio in relation to different anthropometric and prognostic parameters, but also to survival. Our results show that this ratio is significantly influenced by the sex, the hematocrit values, the hemoglobin levels, the beta-2 microglobulin, the red cell distribution width and RDW/albumin ratio. Instead, it is not affected by age, RDW/hemoglobin ratio, LDH values and the bone marrow plasma cell infiltration. Moreover, we observed a marked difference in this ratio between surviving and deceased MM patients. The obtained data, although preliminary, may help to understand the complexity of multiple myeloma, especially in the field of the prognostic evaluation, and they could suggest a role for the albumin/fibrinogen ratio as an additional biomarker of multiple myeloma.

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.

Aims Tyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverse events. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have been used to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulness of the new cardiovascular risk assessment model proposed by the Cardio‐Oncology Study Group of the Heart Failure Association (HFA) of the ESC in collaboration with the International Cardio‐Oncology Society (ICOS) to stratify the cardiovascular risk in CML patients, compared with SCORE risk charts. The secondary aim was to establish the incidence of adverse arterial events (AEs) in patients with CML treated with TKIs and the influence of preventive treatment with aspirin. Methods and results A retrospective single‐centre observational study was carried out on 58 patients (32 men and 26 women; mean age ± SD: 59 ± 15 years) with CML treated with TKIs for a median period of 43 ± 31 months. Cardiological evaluation was performed and cardiovascular risk was estimated with SCORE risk charts and with the new risk assessment tool proposed by HFA/ICOS. AEs were recorded. According to SCORE charts and the new HFA/ICOS risk stratification tool, respectively, 46% (Group A1) and 60% (Group A2) of patients were at high–very high risk, and 54% (Group B1) and 40% (Group B2) at low–moderate risk. AEs were significantly more frequent in Group A1 than Group B1 (P value < 0.01) when considered overall; they were significantly more frequent in Group A2 than Group B2 either overall or considered individually. HFA/ICOS risk stratification tool was significantly more sensitive than SCORE (P < 0.01) in identifying patients at higher risk of cardiovascular toxicity. In addition, we did not find AEs in patients pretreated with aspirin. Conclusions The new HFA/ICOS risk stratification model allows a more tailored cardiovascular risk stratification in patients with CML and it is more sensitive than SCORE charts.

Rituximab is employed in the treatment of B-cell non-Hodgkin lymphomas (NHL) and autoimmune disorders of hematological interest (ADHI), such as autoimmune hemolytic anemia (AIHA), acquired hemophilia A (AHA), and immune thrombocytopenia (ITP). Rituximab induces profound B-cell depletion, reducing the titer of immunoglobulins and autoreactive antibodies, but secondary hypogammaglobulinemia increases risk of infections. We performed a retrospective, multicentric study across seven Italian centers to compare two cohorts of patients with either indolent NHL or ADHI treated with rituximab between March 2014 and March 2024. We evaluated the incidence and characteristics of infections and common antimicrobial prophylaxis adopted according to local clinical practice, in the absence of shared guidelines for ADHI. We included 285 patients (52% female; median age 55 years). The ADHI cohort comprised 187 patients (65%; 97 ITP, 78 AIHA, 12 AHA), while the control group included 98 i-NHL patients (34%). We documented 65 infectious events occurring in 65/285 patients (22.8%). Infection-related mortality occurred in 9 patients (4%). When stratified, the cumulative 180-day incidence of infections was 9.4% (IC95% 8.8%-10%) for NHL patients and 13.7% for ADHI (IC95% 12.2%-14.2%). Multivariate analysis identified prophylaxis (OR 2.62, p  = 0.014) and post-treatment hypogammaglobulinemia (OR 2.73 p  = 0.004) as risk factors. The risk of infection in patients with ADHI is high and comparable to that observed in NHL. Therefore, close monitoring of IgG levels is strongly advised, and mortality can be contained through rigorous antimicrobial stewardship.

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly evaluated. The presence of aPL in patients with ITP should be assessed as well to stratify the risk of paradoxical thrombosis. In detail, besides the high hemorrhagic risk in secondary thrombocytopenia, patients with a co-diagnosis of APS or only antibodies are also at risk of arterial and venous thrombosis. In this narrative review, we discuss the correlation between APS and ITP, the mechanisms behind the above-reported entities, in order to support clinicians to define the most appropriate treatment strategy in these patients, especially when anticoagulant or antiplatelet agents may be needed.

Multiple myeloma (MM) remains incurable despite effective therapies, with most patients eventually relapsing. Chimeric antigen receptor (CAR) T-cell therapy has improved treatment options but is limited by antigen escape and lack of durable responses. To expand the spectrum of actionable antigens, we sought to identify novel CAR-T actionable targets. We analyzed 11 publicly available single-cell RNA sequencing datasets from patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering MM (SMM), MM, relapsed/refractory MM (RRMM) and healthy donors. Plasma cell-specific surface proteins were identified via bioinformatic filtering and validated on external bulk transcriptomic database of ~2,000 patients and by flow cytometry on MM cell lines and primary bone marrow samples. We identified 15 plasma cell-associated surface proteins, including BCMA, CD138, CD38, and SLAMF7. Five molecules-TNFRSF13B (TACI), CD59, FCGR2B (CD32B), SLC44A1 (CD92), and CD320-were prioritized for further study. CD320 and SLC44A1 were upregulated with disease stage and associated with poor survival, while TNFRSF13B, CD59, and FCGR2B were enriched in advanced disease and linked to better outcomes. Cytogenetic clustering linked these molecules to specific genetic backgrounds, suggesting subtyperelated expression patterns. Flow cytometry confirmed the surface expression of CD59, SLC44A1, TNFRSF13B and CD320. CD320, SLC44A1, and TNFRSF13B are promising, clinically relevant targets for CAR T-cell therapy in MM. Their stage-specific expression and prognostic significance support their potential to enhance existing immunotherapeutic strategies.

The pathogenesis of venous thromboembolism in multiple myeloma is still poorly understood because multiple factors are involved. In particular, the increase in whole blood viscosity has a key role and, therefore, we performed an evaluation of some hemorheological determinants in multiple myeloma patients, putting them in relation to the thrombotic risk, with the aim to evaluate if an alteration of the hemorheological pattern was associated with a higher thrombotic risk. We performed an observational retrospective cohort study with data collected from January 2017 to September 2022. In a group of 190 patients with newly diagnosed multiple myeloma, we have examined the trend of calculated blood viscosity according to the Merrill formula, and we stratified the patients for the thrombotic risk in accordance with the IMWG/NCCN guidelines and with IMPEDE VTE score. Using the thrombotic risk stratification proposed by IMWG/NCCN any variation in calculated blood viscosity is evident, while, with the IMPEDE VTE score, we observed an increase in calculated blood viscosity in patients with “intermediate + high” risk. The calculated blood viscosity is higher in subjects presenting an “intermediate + high” thrombotic risk according to the IMPEDE VTE score. This association could therefore lay the groundwork for further research with the aim to confirm the role of hemorheological pattern in MM-related thrombotic risk.

Background: In this single center study, we retrospectively evaluated the calculated hemorheological profile in patients with a new diagnosis of multiple myeloma, with the aim to evaluate possible relationships with some prognostic predictors, such as ISS, albumin levels, beta2-microglobulin, red cell distribution width, and bone marrow plasma cell infiltration. Methods: In a cohort of 190 patients, we examined the calculated blood viscosity using the de Simone formula, and the albumin/fibrinogen ratio as a surrogate of erythrocyte aggregation, and then we related these parameters to prognostic factors, using the Kruskal–Wallis and the Mann–Whitney tests, respectively. Results: From our analysis, it emerged that the evaluated hemorheological pattern differed in the three isotypes of multiple myeloma, and the whole blood viscosity was higher in IgA and IgG isotypes with respect to the light chain multiple myeloma (p < 0.001). Moreover, we observed that, as the ISS stage progressed, the albumin/fibrinogen ratio was reduced, and the same hemorheological trend was traced in subgroups with lower albumin levels, higher beta2-microglobulin and red cell distribution width RDW values, and in the presence of a greater bone marrow plasma cell infiltrate. Conclusions: Through the changes in blood viscosity in relation to different prognostic factors, this analysis might underline the role of the hemorheological pattern in multiple myeloma.

Since neutrophil extracellular traps formation (NET-osis) can be assessed indirectly by treating healthy neutrophils with blood-derived fluids from patients and then measuring the NETs response, we designed a pilot study to convey high-dimensional cytometry of peripheral blood immune cells and cytokines, combined with clinical features, to understand if NET-osis assessment could be included in the immune risk profiling to early prediction of clinical patterns, disease severity, and viral clearance at 28 days in COVID-19 patients. Immune cells composition of peripheral blood, cytokines concentration and in-vitro NETosis were detected in peripheral blood of 41 consecutive COVID-19 inpatients, including 21 mild breakthrough infections compared to 20 healthy donors, matched for sex and age. Major immune dysregulation in peripheral blood in not-vaccinated COVID-19 patients compared to healthy subjects included: a significant reduction of percentage of unswitched memory B-cells and transitional B-cells; loss of naïve CD3 + CD4 + CD45RA + and CD3 + CD8 + CD45RA + cells, increase of IL-1β, IL-17A and IFN-γ. Myeloid compartment was affected as well, due to the increase of classical (CD14 ++ CD16 − ) and intermediate (CD14 ++ CD16 + ) monocytes, overexpressing the activation marker CD64, negatively associated to the absolute counts of CD8+ CD45R0+ cells, IFN-γ and IL-6, and expansion of monocytic-like myeloid derived suppressor cells. In not-vaccinated patients who achieved viral clearance by 28 days we found at hospital admission lower absolute counts of effector cells, namely CD8 + T cells, CD4 + T-cells and CD4 + CD45RO + T cells. Percentage of in-vitro NET-osis induced by patients’ sera and NET-osis density were progressively higher in moderate and severe COVID-19 patients than in mild disease and controls. The percentage of in-vitro induced NET-osis was positively associated to circulating cytokines IL-1β, IFN-γ and IL-6. In breakthrough COVID-19 infections, characterized by mild clinical course, we observed increased percentage of in-vitro NET-osis, higher CD4+ CD45RO+ and CD8+ CD45RO+ T cells healthy or mild-COVID-19 not-vaccinated patients, reduced by 24 h of treatment with ACE inhibitor ramipril. Taken together our data highlight the role of NETs in orchestrating the complex immune response to SARS-COV-2, that should be considered in a multi-target approach for COVID-19 treatment.