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Abstract Aims Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy. Methods Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion. The study endpoints were i) incidence of cancer therapy-related cardiac dysfunction (CTRCD), CTRCD were also balanced for any grade CRS, but CTRCD occurred of Cardiology Guidelines on Cardio-Oncology (decrements of left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and/or elevations of cardiac biomarkers (high sensitivity troponin I, natriuretic peptides) and ii), correlations of echocardiographic metrics with inflammatory biomarkers. Results Incidence of CTRCD was high at 7 days (59,3%), particularly in subjects with CRS. The integrated definition of CTRCD allowed the identification of the majority of cases (50%). Moreover, early LVEF and GLS decrements were inversely correlated with fibrinogen and interleukin-2 receptor levels (p always ≤ 0.01). Conclusions There is a high incidence of early CTRCD in patients treated with CAR-T cells, and a link between CTRCD and inflammation can be demonstrated. Dedicated patient monitoring protocols are advised. Graphical Abstract

Patients with hematological malignancies (HMs) are at high risk of respiratory viral infections due to the intrinsic deterioration of the immune system and chemotherapy treatments. In the recent past, SARS-CoV-2 respiratory viral infection has been responsible for most infectious complications in HMs. We analyzed 2950 samples from 505 patients admitted to the Hematology department from 2019 to 2023. The aim of this study was to determine the epidemiological trend of respiratory viruses in the SARS-CoV-2 era, the characteristics of the patients involved and their outcomes. In our analysis, we found a reduction in non-SARS-CoV-2 respiratory viral (NSRV) positivity during the pandemic period, although these data did not show statistical significance. Most of the HMs involved were Multiple Myeloma and Acute Myeloid Leukemia. Overall mortality rate was very low and characterized by the progression of the HMs as well as the worsening of respiratory failure. In conclusion, a reduction in non-COVID viral infections was highlighted, probably also thanks to the increase in prevention measures and environmental modifications of the viral background.

Flow cytometry (FCM) and quantitative PCR (qPCR) are conventional methods for assessing CAR-T expansion, while digital droplet PCR (ddPCR) is emerging as a promising alternative. We monitored CAR-T transcript expansion in 40 B-NHL patients post-infusion of CAR-T products (axi-cel; tisa-cel; and brexu-cel) with both His-Tag FCM and ddPCR techniques. Sensitivity and predictive capacity for efficacy and safety outcomes of ddPCR were analyzed and compared with FCM. A significant correlation between CAR-T counts determined by FCM and CAR transcripts assessed by ddPCR (p < 0.001) was observed. FCM revealed median CD3+CAR+ cell counts at 7, 14, and 30 days post-infusion with no significant differences. In contrast, ddPCR-measured median copies of CAR-T transcripts demonstrated significant lower copy numbers in tisa-cel recipients compared to the other products at day 7 and day 14. Patients with a peak of CAR transcripts at day 7 exceeding 5000 copies/microg gDNA, termed “good CAR-T expanders”, were more likely to achieve a favorable response at 3 months (HR 10.79, 95% CI 1.16–100.42, p = 0.036). Good CAR-T expanders showed superior progression-free survival at 3, 6, and 12 months compared to poor CAR-T expanders (p = 0.088). Those reaching a peak higher than 5000 copies/microg gDNA were more likely to experience severe CRS and ICANS. DdPCR proves to be a practical method for monitoring CAR-T expansion, providing quantitative information that better predicts both treatment outcomes and toxicity.

BackgroundMalignancies represent 15–50% of total causes of pericardial effusions (PE). Routine analyses recommended to be performed on pericardial fluid include general chemistry, cytology, polymerase chain reaction, and microbiological cultures. Multicolor flow cytometry (FC) is a laboratory test that already proved to be useful in the detection of lymphoproliferative and metastatic malignancies in pleural and peritoneal effusions, but current guidelines do not mention its use on PE to reach a diagnosis.MethodsOur institutional protocol foresees to routinely perform a multicolor FC analysis on pericardial fluid samples obtained by pericardiocentesis, in addition to other guidelines-recommended analyses. A sample of 15–30 ml is analyzed using a lyse and wash staining method using combination panels of antibodies, allowing to detect specific cellular subpopulations, analyzing tens to hundreds of thousands of cells in few seconds. The present manuscript aims to report our single-center experience with this diagnostic tool in patients presenting with PE requiring pericardiocentesis.ResultsRoutine use of multicolor FC on pericardial fluid samples in our institution allowed to reach a definite diagnosis of cardiac lymphomas in two patients presenting with otherwise unexplained severe PE. This resulted in immediate start of combined immunotherapy, with patients’ clinical improvement. At 6 months follow-up both patients are alive and presented a complete disease regression.ConclusionPreliminary evidence from routine use of multicolor FC on PE support that this is a promising tool to reach a rapid diagnosis of hematological malignancies with heart involvement, leading to a prompt initiation of targeted therapies.

Chimeric antigen receptor (CAR) T cells represent one of the newest frontiers of cell therapy. Their application currently involves relapsed/refractory aggressive B cell lymphoma and leukemia as a standard of care, while several studies are exploring CAR-T to treat multiple myeloma and other hematological malignancies. Here we describe the cytomorphology of CAR-T collected from the leftovers of infusion bags, and therefore before the encounter with the antigen, with, among others, a peculiar population of giant lymphoid cells with blastoid features and hypertrophic centrosome.