In patients with COIVD‐19, in the early aggravation phase before treatment, observation of peripheral blood film shows the presence of pronounced morhological anomalies of the granulocyte series. One week after the start of treatment, such anomalies subside, and an increasing proportion of reactive lymphocytes dominates.

Summary: A low count of CD4⁺ and CD8⁺ lymphocytes is a hallmark laboratory finding in the coronavirus disease 2019 (COVID‐19). Using flow cytometry, we observed significantly higher CD95 (Fas) and PD‐1 expression on both CD4⁺ T and CD8⁺ T cells in 42 COVID‐19 patients when compared to controls. Higher CD95 expression in CD4⁺ cells correlated with lower CD4⁺ counts. A higher expression of CD95 in CD4⁺ and CD8⁺ lymphocytes correlated with a lower percentage of naive events. Our results might suggest a shift to antigen‐activated T cells, expressing molecules increasing their propensity to apoptosis and exhaustion during COVID‐19 infection.

Summary: CD4⁺ and CD8⁺ chimeric antigen receptor T cells (CAR‐T) play different roles in the in vivo anti‐tumour response, but the role of the CD4⁺/CD8⁺ ratio among infused CAR‐T has not been clearly defined yet. We analysed leftovers from infused anti‐CD19 CAR‐T bags of 31 patients with aggressive B‐cell lymphomas. The median ratio was 1.44, lower for brexu‐cel compared to tisa‐cel and axi‐cel. The CAR+CD4⁺/CD8⁺ ratio was influenced by lactate dehydrogenase levels at apheresis, not by age, previous treatments or the CD4⁺/CD8⁺ ratio in peripheral blood. Patients with a response at 3 months after CAR‐T (M3) had a lower CAR+CD4⁺/CD8⁺ ratio in the infused products compared to non‐responders (ratio 0.74 vs. 2.47, p = 0.011). A CAR+CD4⁺/CD8⁺ ratio higher than the cut point of 1.12 was associated with an increased risk of treatment failure at M3 (OR 23.3, p = 0.012) and M6 (OR 10, p = 0.028). The median 6‐month PFS was 76% for patients with a ratio lower than 1.12% vs. 31% for the others. The prognostic role of the CAR+CD4⁺/CD8⁺ ratio was independent of the costimulatory domain (CD28 vs. 4‐1BB) of the product (OR 16.41, p = 0.041). Our data indicate a crucial role for CD8⁺ CAR‐T and the CAR+CD4⁺/CD8⁺ ratio in predicting CAR‐T efficacy.

Lymphoma is listed among the neoplasias with a high risk of venous thromboembolism (VTE). Risk factors for VTE appear to differ from risk factors in solid tumors. We review the literature of the last 20 years for reports identifying these risk factors in cohorts consisting exclusively of lymphoma patients. We selected 25 publications. The most frequent studies were analyses of retrospective single-center cohorts. We also included two reports of pooled analyses of clinical trials, two meta-analyses, two analyses of patient registries, and three analyses of population-based databases. The VTE risk is the highest upfront during the first two months after lymphoma diagnosis and decreases over time. This upfront risk may be related to tumor burden and the start of chemotherapy as contributing factors. Factors consistently reported as VTE risk factors are aggressive histology, a performance status ECOG ≥ 2 leading to increased immobility, more extensive disease, and localization to particular sites, such as central nervous system (CNS) and mediastinal mass. Association between laboratory values that are part of risk assessment models in solid tumors and VTE risk in lymphomas are very inconsistent. Recently, VTE risk scores for lymphoma were developed that need further validation, before they can be used for risk stratification and primary prophylaxis. Knowledge of VTE risk factors in lymphomas may help in the evaluation of the individual risk-benefit ratio of prophylaxis and help to design prospective studies on primary prophylaxis in lymphoma.

Since the introduction of rituximab in the late 1990s, significant progress has been made in advancing targeted therapies for B cell lymphomas, improving patients’ chance of being cured and clinicians’ therapeutic armamentarium. A better understanding of disease biology and pathogenic pathways, coupled with refinements in immunophenotypic and molecular diagnostics, have been instrumental in these achievements. While traditional chemotherapy remains fundamental in most cases, concerns surrounding chemorefractoriness and cumulative toxicities, particularly the depletion of the hemopoietic reserve, underscore the imperative for personalized treatment approaches. Integrating targeted agents, notably monoclonal antibodies, alongside chemotherapy has yielded heightened response rates and prolonged survival. A notable paradigm shift is underway with innovative-targeted therapies replacing cytotoxic drugs, challenging conventional salvage strategies like stem cell transplantation. This review examines the landscape of emerging targets for lymphoma cells and explores innovative therapies for diffuse large B cell lymphoma (DLBCL). From Chimeric Antigen Receptor-T cells to more potent monoclonal antibodies, antibody–drug conjugates, bispecific antibodies, checkpoint inhibitors, and small molecules targeting intracellular pathways, each modality offers promising avenues for therapeutic advancement. This review aims to furnish insights into their potential implications for the future of DLBCL treatment strategies.

Impaired function of hematopoiesis after treatment with chimeric antigen T‐cells (CAR‐T) is a frequent finding and can interest a wide range of patients, regardless of age and underlying disease. Trilinear cytopenias, as well as hypogammaglobulinemia, B‐cell aplasia, and T‐cell impairment, can severely affect the infectious risk of CAR‐T recipients, as well as their quality of life. In this review, we provide an overview of defects in hematopoiesis after CAR‐T, starting with a summary of different definitions and thresholds. We then move to summarize the main pathogenetic mechanisms of cytopenias, and we offer insight into cytomorphological aspects, the role of clonal hematopoiesis, and the risk of secondary myeloid malignancies. Subsequently, we expose the major findings and reports on T‐cell and B‐cell quantitative and functional impairment after CAR‐T. Finally, we provide an overview of current recommendations and leading experiences regarding the management of cytopenias and defective B‐ and T‐cell function.