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Cell therapies, including tumor antigen-loaded dendritic cells used as therapeutic cancer vaccines, offer treatment options for patients with malignancies. We evaluated the feasibility, safety, immunogenicity, and clinical activity of adjuvant vaccination with Wilms’ tumor protein (WT1) mRNA-electroporated autologous dendritic cells ( WT1 -mRNA/DC) in a single-arm phase I/II clinical study of patients with advanced solid tumors receiving standard therapy. Disease status and immune reactivity were evaluated after 8 weeks and 6 months. WT1 -mRNA/DC vaccination was feasible in all patients, except one. Vaccination was well tolerated without evidence of systemic toxicity. The disease control rate and overall response rate among a total of 39 evaluable patients were 74.4% and 12.8%, respectively. Median overall survival (OS) was 43.7 months among 13 patients with glioblastoma multiforme, 41.9 months among 12 patients with metastatic breast cancer, and 48.8 months among 10 patients with malignant pleural mesothelioma, comparing favourably with historical controls reported in the literature. OS was longer in patients with stable disease at 8 weeks and disease control at 6 months versus patients without disease control at either time point. Disease control and higher OS were associated with antigen-specific type 1 CD4 + and/or CD8 + T-lymphocyte responses, mainly induced by WT1 -mRNA/DC vaccination. Antigen-nonspecific type 2 CD8 + T-cell responses were common before WT1 -mRNA/DC vaccination but did not show any association with clinical outcome. Collectively, these data indicate that WT1 -mRNA/DC vaccination is feasible, safe, and immunogenic and shows clinical activity in patients with advanced solid tumors, suggesting that it has the potential to help improve their survival.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease–associated pulmonary aspergillosis (CAPA). We found 10%–15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%–52%.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

We performed an observational study to investigate intensive care unit incidence, risk factors, and outcomes of coronavirus disease-associated pulmonary aspergillosis (CAPA). We found 10%-15% CAPA incidence among 823 patients in 2 cohorts. Several factors were independently associated with CAPA in 1 cohort and mortality rates were 43%-52%.

We report the case of a 34-year old patient presenting with multiple osteolytic bone laesions and hypercalcaemia due to Philadelphia chromosome positive B-cell acute lymphoblastic leukaemia (B-ALL). Given this atypical presentation with absence of peripheral blastosis and normal blood cell count besides mild thrombocytopenia, diagnosis of B-ALL in these subset of patients is often challenging. Osteolytic bone laesions and hypercalcaemia are frequently seen in adult acute T-cel leukaemia and childhood B-ALL but represent highly uncommon presentations of B-ALL in adults. Searching literature we found only 4 cases reported worldwide. In children the subset of patients with B-ALL and hypercalcaemia often display similar characteristics including 'aleukemic' presentation (normale white blood cell count without peripheral blastosis) and the absence of organomegaly and lymphadenopathy. The underlying mechanism of hypercalcaemia in B-ALL in incompletely understood. Several data suggest these symptoms being caused by the production of humoral tumor-derived factors increasing osteoclast activity (e.g. parathyroid hormone related protein (PTHrP), interleukin-1, interleukin-6, interleukin-11 and tumor necrosis factor alpha and beta). Lymphoblasts have been shown to actively produce PTHrP stimulating bone resorption, renal calcium resorption and renal phosphate excretion via binding the PTH/PTHrP-receptor. Although elevated serum levels of PTHrP have been detected in the majority of paediatric leukaemic patients with hypercalcemia, elevated serum levels of PTHrP without hypercalcaemia in asymptomatic carriers of HTLV-1 (human T-lymphotrophic virus 1) suggest that PTHrP isn't the sole responsible mechanism. Moreover in patients with B-ALL and hypercalcaemia, PTHrP isn't always elevated. More research needs to be done to outline underlying pathophysiology. Hypercalcaemia due to osteolytic bone laesions is a highly uncommon yet potentially life threatening presentation of adult B-ALL and clinical awareness is therefore mandatory. Our patient was immediately treated with zolendronic acid, high dose corticoids and induction chemotherapy which resulted in normalisation of calcaemic levels an resolution of pain symptoms.