Highlights Higher mortality rate in COVID-19 patients with haematologic diseases. Haematologic patients with COVID-19 have 50 % less chance of survival. Probability of death was higher in patients older than 40 yrs of age with AML/MDS.

The dysregulation of both the innate and adaptive responses to SARS-CoV-2 have an impact on the course of COVID-19, and play a role in the clinical outcome of the disease. Here, we performed a comprehensive analysis of peripheral blood lymphocyte subpopulations in 82 patients with COVID-19, including 31 patients with a critical course of the disease. In COVID-19 patients who required hospitalization we analyzed T cell subsets, including Treg cells, as well as TCRα/β and γ/δ, NK cells, and B cells, during the first two weeks after admission to hospital due to the SARS-CoV-2 infection, with marked reductions in leukocytes subpopulations, especially in critically ill COVID-19 patients. We showed decreased levels of Th, Ts cells, Treg cells (both naïve and induced), TCRα/β and γ/δ cells, as well as CD16+CD56+NK cells in ICU compared to non-ICU COVID-19 patients. We observed impaired function of T and NK cells in critically ill COVID-19 patients with extremely low levels of secreted cytokines. We found that the IL-2/INFγ ratio was the strongest indicator of a critical course of COVID-19, and was associated with fatal outcomes. Our findings showed markedly impaired innate and adaptive responses in critically ill COVID-19 patients, and suggest that the immunosuppressive state in the case of a critical course of SARS-CoV-2 infection might reflect subsequent clinical deterioration and predict a fatal outcome.

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B-cell chronic lymphocytic leukemia (B-CLL) presents with progressive accumulation of monoclonal B cells in the peripheral blood, bone marrow and lymphoid organs. B-CLL is characterized by heterogeneous clinical outcome. The expression of Toll-like receptors (TLRs) and their association with other prognostic factors in B-CLL patients remain unclear. The aim of our study was to evaluate the expression of TLR2, TLR4 and TLR9 genes and their significance as biological markers in patients with B-CLL. Sixty patients with newly diagnosed B-CLL were evaluated. The healthy control group included 20 age-matched individuals. Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. TLR4 gene expression was lower in B-CLL patients as compared to the control group and TLR2 gene expression was higher in B-CLL patients than in healthy individuals. TLR9 gene expression was higher in the control group than in patients with B-CLL. TLR4 mRNA expression was lower in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early stage disease (Rai stages 0–II). TLR2 gene expression was higher in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early stage disease (Rai stages 0–II; p < 0.05). Our results suggest that TLRs could become potential biological markers for the clinical outcome in patients with B-CLL.

Severe treatment-refractory T-cell-mediated immune skin toxicities observed with obinutuzumab/ rituximab-atezo-pola in two patients with follicular lymphomaThe immune cell microenvironment strongly influences outcome in follicular lymphoma (FL). Checkpoint inhibitors (CPI) and other cancer immunotherapy agents in combination with standard-of-care anti-CD20 antibodies (obinutuzumab [G] or rituximab [R]) are currently being evaluated in FL; a phase 1/2 trial in relapsed/refractory (R/R) FL (BO29561; NCT02729896), is evaluating G or R combined with the anti-programmed death-ligand 1 (PD-L1) antibody, atezolizumab, and the anti-CD79b antibody-drug conjugate, polatuzumab vedotin (G/R-atezo-pola). An ongoing phase 1b study has demonstrated the activity and low rate of immune-mediated toxicities with G-atezo in R/R non-Hodgkin lymphoma. 1 Furthermore, two phase 1b/2 studies in R/R FL and diffuse large B-cell lymphoma (DLBCL) have reported acceptable safety profiles with G-pola. 2,3 CPI are associated with specific immune-related toxicities that mainly involve the gut, skin, endocrine glands, kidneys, liver and lungs. 4 Guidelines from the American Society of Clinical Oncology suggest that these events are manageable with corticosteroids.Among 13 R/R FL and 21 R/R DLBCL patients treated with G-atezo-pola and R-atezo-pola, respectively, in the BO29561 trial, we present two case reports of R/R FL patients who died while experiencing drug-related toxicity. Patients experienced a constellation of immune toxihaematologica 2020; 105:e256 CASE REPORTS