The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Proteomic Landscape of Extracellular Vesicles for Diffuse Large B-Cell Lymphoma Subtyping.

The role of extracellular vesicles (EVs) proteome in diffuse large B-cell lymphoma (DLBCL) pathology, subclassification, and patient screening is unexplored. We analyzed by state-of-the-art mass spectrometry the whole cell and secreted extracellular vesicles (EVs) proteomes of different molecular subtypes of DLBCL, germinal center B cell (GCB subtype), and activated B cell (ABC subtype). After quality control assessment, we compared whole-cell and secreted EVs proteomes of the two cell-of-origin (COO) categories, GCB and ABC subtypes, resulting in 288/1115 significantly differential expressed proteins from the whole-cell proteome and 228/608 proteins from EVs (adjust p-value < 0.05/p-value < 0.05). In our preclinical model system, we demonstrated that the EV proteome and the whole-cell proteome possess the capacity to separate cell lines into ABC and GCB subtypes. KEGG functional analysis and GO enrichment analysis for cellular component, molecular function, and biological process of differential expressed proteins (DEP) between ABC and GCB EVs showed a significant enrichment of pathways involved in immune response function. Other enriched functional categories for DEPs constitute cellular signaling and intracellular trafficking such as B-cell receptor (BCR), Fc_gamma R-mediated phagocytosis, ErbB signaling, and endocytosis. Our results suggest EVs can be explored as a tool for patient diagnosis, follow-up, and disease monitoring. Finally, this study proposes novel drug targets based on highly expressed proteins, for which antitumor drugs are available suggesting potential combinatorial therapies for aggressive forms of DLBCL. Data are available via ProteomeXchange with identifier PXD028267.

Age-adjusted international prognostic index is a predictor of survival in gastric diffuse B-cell non-Hodgkin lymphoma patients

Background The clinical course of gastric lymphoma is heterogeneous and clinical symptoms and some factors have been related to prognosis. Objective The present study aims to identify prognostic factors in gastric diffuse B-cell non-Hodgkin lymphoma diagnosed and treated in different countries. Methods A consecutive series of gastric diffuse B-cell non-Hodgkin lymphoma patients diagnosed and treated in Brazil, Portugal and Italy, between February 2008 and December 2014 was evaluated. Results Of 104 patients, 57 were female and the median age was 69 years (range: 28­88). The distribution of the age-adjusted international prognostic index was 12/95 (13%) high risk, 20/95 (21%) high-intermediate risk and 63/95 (66%) low/low-intermediate risk. Symptoms included abdominal pain (63/74), weight loss (57/73), dysphagia (37/72) and nausea/vomiting (37/72). Bulky disease was found in 24% of the cases, anemia in 33 of 76 patients and bleeding in 22 of 72 patients. The median follow-up time was 25 months (range: 1­77 months), with 1- and 5-year survival rates of 79% and 76%, respectively. The multivariate Cox Regression identified the age-adjusted international prognostic index as a predictor of death (hazard risk: 3.62; 95% confidence interval: 2.21­5.93; p-value <0.0001). Conclusions This series identified the age-adjusted international prognostic index as predictive of mortality in patients treated with conventional immunochemotherapy.

Identification of a panel of ten cell surface protein antigens associated with immunotargeting of leukemias and lymphomas by peripheral blood gammadelta T cells.

BACKGROUND: Vgamma9Vdelta2 T lymphocytes are regarded as promising mediators of cancer immunotherapy due to their capacity to eliminate multiple experimental tumors, particularly within those of hematopoietic origin. However, Vgamma9Vdelta2 T-cell based lymphoma clinical trials have suffered from the lack of biomarkers that can be used as prognostic of therapeutic success. DESIGN AND METHODS: We have conducted a comprehensive study of gene expression in acute lymphoblastic leukemias and non-Hodgkin's lymphomas, aimed at identifying markers of susceptibility versus resistance to Vgamma9Vdelta2 T cell-mediated cytotoxicity. We employed cDNA microarrays and quantitative real-time PCR to screen 20 leukemia and lymphoma cell lines, and 23 primary hematopoietic tumor samples. These data were analyzed using state-of-the-art bioinformatics, and gene expression patterns were correlated with susceptibility to Vgamma9Vdelta2 T cell mediated cytolysis in vitro. RESULTS: We identified a panel of 10 genes encoding cell surface proteins that were statistically differentially expressed between "gammadelta-susceptible" and "gammadelta-resistant" hematopoietic tumors. Within this panel, 3 genes (ULBP1, TFR2 and IFITM1) were associated with increased susceptibility to Vgamma9Vdelta2 T-cell cytotoxicity, whereas the other 7 (CLEC2D, NRP2, SELL, PKD2, KCNK12, ITGA6 and SLAMF1) were enriched in resistant tumors. Furthermore, some of these candidates displayed a striking variance of expression among primary follicular lymphomas and T-cell acute lymphoblastic leukemias. CONCLUSIONS: Our results suggest that hematopoietic tumors display a highly variable repertoire of surface proteins that can impact on Vgamma9Vdelta2 cell-mediated immunotargeting. The prognostic value of the proposed markers can now be evaluated in upcoming Vgamma9Vdelta2 T cell-based lymphoma/leukemia clinical trials.

Long-term follow-up of lymphocyte populations and cellular cytokine production in patients with chronic graft-versus-host disease treated with extracorporeal photopheresis.

We studied lymphocyte populations and cytokine-expression profiles of ten patients with chronic graft-versus-host disease who at least transiently responded to photoimmunotherapy. The numbers of lymphocytes, monocytes and dendritic cells rose in most cases. Th1 cells always increased during therapy, supporting the hypothesis that a more favorable immune balance contributes to clinical responses.