During the last decade the field of cancer immunotherapy has witnessed impressive progress. Highly effective immunotherapies such as immune checkpoint inhibition, and T-cell engaging therapies like bispecific T-cell engaging (BiTE) single-chain antibody constructs and chimeric antigen receptor (CAR) T cells have shown remarkable efficacy in clinical trials and some of these agents have already received regulatory approval. However, along with growing experience in the clinical application of these potent immunotherapeutic agents comes the increasing awareness of their inherent and potentially fatal adverse effects, most notably the cytokine release syndrome (CRS). This review provides a comprehensive overview of the mechanisms underlying CRS pathophysiology, risk factors, clinical presentation, differential diagnoses, and prognostic factors. In addition, based on the current evidence we give practical guidance to the management of the cytokine release syndrome.

Summary Objectives Patients with acute respiratory distress syndrome (ARDS) due to viral infection are at risk for secondary complications like invasive aspergillosis. Our study evaluates coronavirus disease 19 (COVID‐19) associated invasive aspergillosis at a single centre in Cologne, Germany. Methods A retrospective chart review of all patients with COVID‐19 associated ARDS admitted to the medical or surgical intensive care unit at the University Hospital of Cologne, Cologne, Germany. Results COVID‐19 associated invasive pulmonary aspergillosis was found in five of 19 consecutive critically ill patients with moderate to severe ARDS. Conclusion Clinicians caring for patients with ARDS due to COVID‐19 should consider invasive pulmonary aspergillosis and subject respiratory samples to comprehensive analysis to detect co‐infection.

IntroductionAllogeneic hematopoietic stem cell transplantation (HSCT) is an established, potentially curative treatment modality for malignant and nonmalignant hematologic diseases. Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after allogeneic HSCT and limits its wider use. Traditionally, GVHD has been divided into 2 forms, acute and chronic, based on the time of its onset. Acute GVHD has been defined as disease occurring in the first 100 days after transplantation, whereas chronic GVHD occurs after day 100. This arbitrary distinction based on the time of onset fails to reflect the different pathophysiologic mechanisms and clinical manifestations of acute and chronic GVHD, however. Acute GVHD can occur after day 100 in patients who received a nonmyeloablative conditioning regimen or donor lymphocyte infusions. In addition, GVHD with typical clinical features of chronic GVHD can develop well before day 100 and concurrent with acute GVHD. Therefore, the National Institutes of Health consensus development project has defined new criteria for the diagnosis, staging, and response assessment of chronic GVHD. 1,2 Only a few effective therapies are currently available for the treatment of both forms of GVHD. The established immunosuppressive agents are mostly nonspecific and unfortunately associated with severe side effects, in particular the susceptibility to lifethreatening infections. Therefore, novel more selective agents are urgently needed.GVHD is an immune-mediated disease that results from a complex interaction between donor and recipient adaptive immunity. Donor-derived CD4 ϩ and CD8 ϩ T lymphocytes have classically been considered to be the main effector cells mediating GVHD pathogenesis. In fact, removal of T cells from transplant inocula almost completely prevents GVHD from developing, however, at the price of increased incidences of graft rejection and disease recurrence. In recent years, basic and clinical research has provided a more detailed mechanistic understanding of the molecules and cell types involved in the biology of the graft-versushost reaction.Because acute GVHD is thought to be mediated mainly by donor T cells, preventive and therapeutic treatment strategies have focused primarily on the inhibition of T-cell function. Recent animal studies suggest that B cells might also play an important role in the biology of GVHD. Further circumstantial evidence for the involvement of B cells in GVHD pathogenesis comes from reports of successful treatment of GVHD with B-cell depletion. The mechanisms by which B cells contribute to acute and chronic GVHD currently are only incompletely understood. Here, we provide an overview of the experimental and clinical evidence for a pathogenic role of B cells in GVHD and evaluate the implications with regard to B cell-targeted therapies for the treatment of GVHD. We conclude by providing an outlook on novel B cell-specific approaches that might prove beneficial for the treatment of GVHD. B-cell functions in health and diseaseB cells ar...