The European Hematology Exam: The Next Step toward the Harmonization of Hematology Training in Europe No abstract available

Children and Adolescents with Chronic Myeloproliferative Neoplasms: Still an Unmet Biological and Clinical Need? No abstract available

Introducing the HemaSphere Controversies Series No abstract available

Von Willebrand Disease: From In Vivo to In Vitro Disease Models Von Willebrand factor (VWF) plays an essential role in primary hemostasis and is exclusively synthesized and stored in endothelial cells and megakaryocytes. Upon vascular injury, VWF is released into the circulation where this multimeric protein is required for platelet adhesion. Defects of VWF lead to the most common inherited bleeding disorder von Willebrand disease (VWD). Three different types of VWD exist, presenting with varying degrees of bleeding tendencies. The pathophysiology of VWD can be investigated by examining the synthesis, storage and secretion in VWF producing cells. These cells can either be primary VWF producing cells or transfected heterologous cell models. For many years transfected heterologous cells have been used successfully to elucidate many aspects of VWF synthesis. However, those cells do not fully reflect the characteristics of primary cells. Obtaining primary endothelial cells or megakaryocytes with a VWD phenotype, requires invasive procedures, such as vessel collection or a bone marrow biopsy. A more recent and promising development is the isolation of endothelial colony forming cells (ECFCs) from peripheral blood as a true-to-nature cell model. Alternatively, various animal models are available but limiting, therefore, new approaches are needed to study VWD and other bleeding disorders. A potential versatile source of endothelial cells and megakaryocytes could be induced pluripotent stem cells (iPSCs). This review gives an overview of models that are available to study VWD and VWF and will discuss novel approaches that can be considered to improve the understanding of the structural and functional mechanisms underlying this disease.

Minimal Residual Disease Assessment in CLL: Ready for Use in Clinical Routine? The introduction of chemoimmunotherapy and more recently the implementation of novel agents into first-line and relapse treatment have substantially improved treatment outcomes in patients with chronic lymphocytic leukaemia (CLL). With longer progression-free survival and more frequently observed deep remissions there is an emerging need for sensitive methods quantitating residual disease after therapy. Over the last decade, assessment of minimal residual disease (MRD) has increasingly been implemented in CLL trials. The predictive value of MRD status on survival outcomes has repeatedly been proven in the context of chemoimmunotherapy and cellular therapies. Recent data suggests a similar correlation for Bcl-2 inhibitor-based therapy. While the relevance of MRD assessment as a surrogate endpoint in clinical trials is largely undisputed, its role in routine clinical practice has not yet been well defined. This review outlines current methods of MRD detection in CLL and summarizes MRD data from relevant trials. The significance of MRD testing in clinical studies and in routine patient care is assessed and new MRD-guided treatment strategies are discussed.

Are We Ready to Treat Diffuse Large B-cell and High-Grade Lymphoma According to Major Genetic Subtypes? Diffuse Large B-Cell Lymphoma (DLBCL) is a clinically and biologically heterogeneous disease. The revised Classification of Lymphoproliferative diseases published in 2016 (WHO, 2016) refined the previous DLBLC subtypes and identified four categories: DLBCL not otherwise specified (NOS), other lymphomas of large B cells, high grade B-cell lymphoma, and B-cell lymphoma unclassifiable. High grade B-cell lymphomas include the entities carrying MYC, BCL2 and/or BCL6 translocations or cases with blastoid morphology without DH translocations. This classification also acknowledges the cell of origin (COO) classification, that has only a limited impact on the choice of frontline treatment for DLBCL, as most patients still receive R-CHOP chemoimmunotherapy. Attempts to improve the outcomes of specific subgroups, especially COO groups, have so far had limited success. Newer analyses have further subdivided DLBCL into genomically distinct subsets, not yet incorporated in the WHO classification, which may facilitate targeted approaches to therapy. In this review, we discuss the subgroups that are recognized by the WHO 2016 classification, review the newer genomic data, and speculate on how this could alter the treatment landscape of DLBCL in the future. We also discuss novel approaches to salvage therapy in the broad context of the heterogeneity of DLBCL.

Fundamentals for a Systematic Approach to Mild and Moderate Inherited Bleeding Disorders: An EHA Consensus Report Healthy subjects frequently report minor bleedings that are frequently ‘background noise’ of normality rather than a true disorder. Nevertheless, unexpected or unusual bleeding may be alarming. Thus, the distinction between normal and pathologic bleeding is critical. Understanding the underlying pathologic mechanism in patients with an excessive bleeding is essential for their counseling and treatment. Most of these patients with significant bleeding will result affected by non-severe inherited bleeding disorders (BD), collectively denominated mild or moderate BD for their relatively benign course. Unfortunately, practical recommendations for the management of these disorders are still lacking due to the current state of fragmented knowledge of pathophysiology and lack of a systematic diagnostic approach. To address this gap, an International Working Group (IWG) was established by the European Hematology Association (EHA) to develop consensus-based guidelines on these disorders. The IWG agreed that grouping these disorders by their clinical phenotype under the single category of mild-to-moderate bleeding disorders (MBD) reflects current clinical practice and will facilitate a systematic diagnostic approach. Based on standardized and harmonized definitions a conceptual unified framework is proposed to distinguish normal subjects from affected patients. The IWG proposes a provisional comprehensive patient-centered initial diagnostic approach that will result in classification of MBD into distinct clinical-pathological entities under the overarching principle of clinical utility for the individual patient. While we will present here a general overview of the global management of patients with MBD, this conceptual framework will be adopted and validated in the evidence-based, disease-specific guidelines under development by the IWG.

Double Umbilical Cord Blood Transplantation in High-Risk Hematological Patients: A Phase II Study Focusing on the Mechanism of Graft Predominance No abstract available

Nivolumab in Relapsed/Refractory Classical Hodgkin Lymphoma – Extended Follow-up of 30 Patients Treated Within the CheckMate 205 Trial in a Single-Center No abstract available

Acute Myeloid Leukemia with Co-mutated ASXL1 and SRSF2 Exhibits Monocytic Differentiation and has a Mutational Profile Overlapping with Chronic Myelomonocytic Leukemia No abstract available