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Abstract : Coronary artery ectasia (CAE) is defined as the dilation of a segment of a coronary vessel to at least 1.5 times the diameter of its normal adjacent segment. Mean platelet volume (MPV) plays a role in acute coronary syndromes, with high MPV correlating to poor prognosis for acute thrombotic events and CAE. Several studies investigated the relationship between MPV and CAE, resulting in conflicting results. These results led us to systematically review all studies investigating the relationship between MPV and ectatic heart diseases by performing a meta-analysis study in order to report a unified result. This meta-analysis study investigated all case-control articles examining the relationship between MPV and CAE. All studies in the following databases published until January 31, 2018, were investigated: Science Direct, Scopus, PubMed, Google Scholar, and Web of Science. Following a quality control evaluation, 14 articles, all of which were published following studies performed in Turkey from 2007 to 2016, met the criteria for study inclusion. After pooling the results from all of the articles, a total standardized mean difference (SMD) value of 0.584 (95% CI, 0.219, 0.95) was obtained using the D+L pooled SMD, indicating a significant difference (P=0.002) between the two groups, with higher MPV values in ectatic patients when comparing to healthy individuals. Therefore, increased MPV levels were significantly related to CAE, suggesting that platelets, with their inflammatory and thrombotic activities, play a role in this disease. Therefore, anti-platelet and anti-inflammatory therapies may be effective in treating CAE.

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Abstract : Management options for patients with immune thrombocytopenia (ITP) have evolved substantially over the past decades. The American Society of Hematology published a treatment guideline for clinicians referring to the management of ITP in 2011. This evidence-based practice guideline for ITP enables the appropriate treatment of a larger proportion of patients and the maintenance of normal platelet counts. Korean authority operates a unified mandatory national health insurance system. Even though we have a uniform standard guideline enforced by insurance reimbursement, there are several unsolved issues in real practice in ITP treatment. To optimize the management of Korean ITP patients, the Korean Society of Hematology Aplastic Anemia Working Party (KSHAAWP) reviewed the consensus and the Korean data on the clinical practices of ITP therapy. Here, we report a Korean expert recommendation guide for the management of ITP.

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Abstract : Measuring response to chemotherapy is a backbone of the clinical management of patients with acute leukemia. This task has historically relied on the ability to identify leukemic cells among normal bone marrow cells by their morphology. However, more accurate ways to identify leukemic cells have been developed, which allow their detection even when they are present in small numbers that would be impossible to be recognized by microscopic inspection. The levels of such minimal residual disease (MRD) are now widely used as parameters for risk assignment in acute lymphoblastic leukemia (ALL) and increasingly so in acute myeloid leukemia (AML). However, different MRD monitoring methods may produce discrepant results. Moreover, results of morphologic examination may be in stark contradiction to MRD measurements, thus creating confusion and complicating treatment decisions. This review focusses on the relation between results of different approaches to measure response to treatment and define relapse in childhood acute leukemia.

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Abstract : Brentuximab vedotin (BV), a potent antibody-drug conjugate, targets the CD30 antigen. Owing to the remarkable efficacy shown in CD30-positive lymphomas, such as Hodgkin's lymphoma and systemic anaplastic large-cell lymphoma, BV was granted accelerated approval in 2011 by the US Food and Drug Administration. Thereafter, many large-scale trials in various situations have been performed, which led to extensions of the original indication. The aim of this review was to describe the latest updates on clinical trials of BV and the in-practice guidance for the use of BV.

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Abstract : One of the hallmarks of the adaptive immune system is the specificity of B and T cell receptors. Thanks to somatic recombination, a large repertoire of receptors can be generated within an individual that guarantee the recognition of a vast number of antigens. Monoclonal antibodies have limited applicability, given the high degree of diversity among these receptors, in BCR and TCR monitoring. Furthermore, with regard to cancer, better characterization of complex genomes and the ability to monitor tumor-specific cryptic mutations or translocations are needed to develop better tailored therapies. Novel technologies, by enhancing the ability of BCR and TCR monitoring, can help in the search for minimal residual disease during hematological malignancy diagnosis and follow-up, and can aid in improving bone marrow transplantation techniques. Recently, a novel technology known as next generation sequencing has been developed; this allows the recognition of unique sequences and provides depth of coverage, heterogeneity, and accuracy of sequencing. This provides a powerful tool that, along with microarray analysis for gene expression, may become integral in resolving the remaining key problems in hematology. This review describes the state of the art of this novel technology, its application in the immunological and hematological fields, and the possible benefits it will provide for the hematology and immunology community.

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Abstract : Multiple myeloma is a malignancy of B-cells that is characterized by the clonal expansion and accumulation of malignant plasma cells in the bone marrow. This disease remains incurable, and a median survival of 3-5 years has been reported with the use of current treatments. Viral-based therapies offer promising alternatives or possible integration with current therapeutic regimens. Among several gene therapy vectors and oncolytic agents, adenovirus has emerged as a promising agent, and it is already being used for the treatment of solid tumors in humans. The main concern with the clinical use of this vector has been its high immunogenicity; adenovirus is often able to induce a strong immune response in the host. Furthermore, new limitations in the efficacy of this therapy, intrinsic to the nature of tumor cells, have been recently observed. For example, our group showed a strong antiviral phenotype in vitro and in vivo in a subset of tumors, shedding new insights that may explain the partial failure of clinical trials based on this promising new therapy. In this review, we describe novel therapeutic approaches that implement viral-based treatments in hematological malignancies and address the novelty as well as the possible limitations of these new therapies, especially in the context of the use of adenoviral vectors for treating multiple myeloma.

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Abstract : Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal myeloid disorders characterized by hematopoietic insufficiency. As MDS and AML are considered to originate from genetic and molecular defects of hematopoietic stem and progenitor cells (HSPC), the main focus of research in this field has focused on the characterization of these cells. Recently, the contribution of BM microenvironment to the pathogenesis of myeloid malignancies, in particular MDS and AML has gained more interest. This is based on a better understanding of its physiological role in the regulation of hematopoiesis. Additionally, it was demonstrated as a ‘proof of principle’ that genetic disruption of cells of the mesenchymal or osteoblastic lineage can induce MDS, MPS or AML in mice. In this review, we summarize the current knowledge about the contribution of the BM microenvironment, in particular mesenchymal stromal cells (MSC) to the pathogenesis of AML and MDS. Furthermore, potential models integrating the BM microenvironment into the pathophysiology of these myeloid disorders are discussed. Finally, strategies to therapeutically exploit this knowledge and to interfere with the crosstalk between clonal hematopoietic cells and altered stem cell niches are introduced.

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Abstract : Despite significant recent advances in the applicability and outcome following unrelated cord blood transplantation (UCBT), infections remain a major cause of mortality associated with poor immune recovery in the first 6 months after UCBT. Enhanced immune reconstitution not only could improve survival by reduced transplant related mortality, but may also favorably impact on relapse incidence by improved graft-versus-leukemia effects. This review will summarize our current understanding of the biology of immune recovery post-UCBT with an emphasis on adaptive T cell dependent immunity. New efforts to boost immunity will be also highlighted including our own laboratory, where ex vivo T cell expansion is pursued towards adoptive immunotherapy.

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Abstract : Myelodysplastic syndromes (MDS) are a group of clonal disorders arising from hematopoietic stem cells generally characterized by inefficient hematopoiesis, dysplasia in one or more myeloid cell lineages, and variable degrees of cytopenias. Most MDS patients are diagnosed in their late 60s to early 70s. The estimated incidence of MDS in the United States and in Europe are 4.3 and 1.8 per 100,000 individuals per year, respectively with lower rates reported in some Asian countries and less well estimated in other parts of the world. Evolution to acute myeloid leukemia can occur in 10-15% of MDS patients. Three drugs are currently approved for the treatment of patients with MDS: immunomodulatory agents (lenalidomide), and hypomethylating therapy [HMT (decitabine and 5-azacytidine)]. All patients will eventually lose their response to therapy, and the survival outcome of MDS patients is poor (median survival of 4.5 months) especially for patients who fail (refractory/relapsed) HMT. The only potential curative treatment for MDS is hematopoietic cell transplantation. Genomic/chromosomal instability and various mechanisms contribute to the pathogenesis and prognosis of the disease. High throughput genetic technologies like single nucleotide polymorphism array analysis and next generation sequencing technologies have uncovered novel genetic alterations and increased our knowledge of MDS pathogenesis. We will review various genetic and non-genetic causes that are involved in the pathogenesis of MDS.

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Abstract : Natural Killer (NK) cells are the third population of lymphocyte in the mononuclear cell compartment that triggers first-line of defense against viral infection and tumor transformation. Historically, NK cells were thought of as components of innate immunity based on their intrinsic ability to spontaneously kill target cells independent of HLA antigen restriction. However, it is now clear that NK cells are quite sophisticated and use a highly specific and complex target cell recognition receptor system arbitrated via a multitude of inhibitory and activating receptors. Killer cell immunoglobulin-like receptors (KIR) are the key receptors of human NK cells development and function. To date, fourteen distinct KIRs have been identified: eight are inhibitory types, and six are activating types. The number and type of KIR genes present varies substantially between individuals. Inhibitory KIRs recognize distinct motifs of polymorphic HLA class I molecules. Upon engagement of their specific HLA class I ligands, inhibitory KIR dampen NK cell reactivity. In contrast, activating KIRs are believed to stimulate NK cell reactivity when they sense their ligands (unknown). KIR and HLA gene families map to different human chromosomes (19 and 6, respectively), and their independent segregation produces a wide diversity in the number and type of inherited KIR-HLA combinations, likely contributing to overall immune competency. Consistent with this hypothesis, certain combinations of KIR-HLA variants have been correlated with susceptibility to diseases as diverse as autoimmunity, viral infections, and cancer. This review summarizes our emerging understanding of KIR-HLA diversity in human health and disease.