Fatih M. Uckun, M.D., Ph.D, is an Active Member of the American Society for Clinical Investigation (ASCI), an honor society for physician-scientists, and an active member of several professional organizations, including ASCO and AACR. He earned his doctoral degrees at University of Heidelberg in Germany and completed his residency training in Pediatrics, fellowship training in Hematology/Oncology/Blood and Bone Marrow Stem Cell Transplantation, as well as postdoctoral research training in immunology at the University of Minnesota in the US. Dr. Uckun has more than 30 years of professional experience in developmental therapeutics and biopharmaceuticals. Dr. Uckun worked as a Professor of Therapeutic Radiology-Radiation Oncology, Pharmacology, and Pediatrics as well as Director of the Biotherapy Institute at the University of Minnesota (1986-1997), where he became the first recipient of the Endowed Hughes Chair in Biotherapy, and as a Professor of Pediatrics and Head of Translational Research in Leukemia and Lymphoma of the Children’s Center for Cancer and Blood Diseases at the University of Southern California (2009-2015). He has held executive positions in multiple biotechnology companies and has extensive relevant regulatory experience. In particular, he served as the IND-sponsor for experimental drugs and biologics. He has published more than 500 peer-reviewed papers and he has authored numerous review articles and book chapters. He received numerous awards including the Stohlman Memorial Award of the Leukemia Society of America (now known as the Leukemia and Lymphoma Society/LLS), the highest honor given to a Leukemia Society Scholar. He has served as a member of several editorial boards and NIH grant review/special emphasis panels.
Rare anaemia (RA), ORPHA108997, include up to 132 rare and ultra-rare haematological conditions, which embrace a highly heterogeneous group of disorders. These are characterized by anaemia of variable degree, from mild forms to life threatening chronic blood-transfusion dependence, and by complex and often unexplained genotype-phenotype correlations. More than 80% of RA are genetic disorders caused by mutations in more than 70 genes controlling red blood cell (RBC) production and structure. These mutations lead to alterations in haemoglobin (Hb) structure or synthesis, RBC maturation and differentiation, cell membrane structure, and enzyme deficiencies. The balance between haemolysis, mainly in the spleen, and erythropoiesis explains the severity of the anemia and patientâ€™s capability to respond to treatment/s. In this context, differential diagnosis, prognosis and patient stratification are often difficult. Some studies have already demonstrated the usefulness of targeted-NGS (t-NGS) approach in the investigation of specific subtypes of RA. However, the huge amount of data generated by NGS technology and in particular the interpretation of Variants of Unknown (or Uncertain) clinical Significance (VUS) which require additional validation, contribute to the low overall diagnostic rate of genetic strategies. Here we describe the development of strategies for diagnosis of RA at different levels of investigation including innovative technology i.e. ektacytometry for RBC rheological studies, which is available only in few laboratories in the world, NGS molecular analysis of disease-causing variants, and extensive and state of the art functional validation of new genetic variants. Integration of conventional and new diagnostic strategies in a harmonized way is essential for holistic diagnosis of patients affected by RA leading to an adequate prognosis and clinical care of the patient.
Joan-Lluis Vives Corrons is a Professor of Medicine (1976-present) and Head of the Red Blood Cell Pathology Unit (1997 ï¿½present) at the Hospital Clï¿½nic i Provincial (University of Barcelona), with main activity focused on the diagnosis of RBC defects and in the identification of low prevalence anaemias or ï¿½Rare Anaemiasï¿½.Research has mainly based on physiopathology, molecular mechanisms and epidemiology of red blood cell (RBC) disorders due to hereditary enzymopathies (G6PD, PK and others), haemoglobinopathies (Sickle-cell anaemia and thalassaemias) and membrane defects (hereditary spherocytosis elliptocytosis and stomatocytosis).Scientific Trajectory is guaranteed by 326 publications in scientific journals, the participation (as editor or collaborator) in about 25 books of haematology, and by the accomplishment of 43 funded research projects, which have been partially funded by different public health organizations from Spain (Ministry of Health and Education and Science), Catalan Government and European Commission.Since 2002, Dr. Vives is head of the Project ENERCA (European Network for Rare and Congenital Anaemias) funded by the European Commission ï¿½ Executive Agency for Health and Consumers (EAHC). ENERCA intends to contribute to the better knowledge of rare anaemias in Europe, its faster diagnosis, treatment; and epidemiological surveillance (www.enerca.org). Its final objective is the consolidation of a European Reference Network (ERN) of Expert Centres in Rare Anaemias (RA).
Dr.Martin Herrmann first studied chemistry in Würzburg and Erlangen. He then completed his studies in biology at the Friedrich-Alexander-University Erlangen in July 1983 with a diploma. After graduating from the Department of Clinical Immunology and Rheumatology of FAU Erlangen in 1989, he was hired as a post-doc in this department and a one-year study abroad at the University of Alabama, Birmingham, USA. As a result of his habilitation in December 1997, Herrmann was a Privatdozent at the Institute for Clinical Immunology and Rheumatology of the FAU Erlangen and was later appointed as an unscheduled professor. Since his diploma thesis Herrmann has been dealing with a certain type of autoimmune disease , systemic lupus erythematosus ( SLE ). Since then he has worked in projects and collaborations in research in the field of immunology and especially in the research of SLE.
Sickle cell disease (SCD) comprises a group of hemoglobinopathies in which hemoglobin S is expressed. Abnormal adhesion of red blood cells containing HbS (sickle RBCs) has been postulated to be important in the initiation and/or progression of painful vaso-occlusive crises, the hallmark of SCD. Despite worldwide efforts to establish therapeutic strategies to prevent vaso-occlusion in SCD, the resulting acute pain crises and end-organ damage remain a high burden for public health due to the lack of effective treatments. Additionally, there are no therapies against sickle cell signaling mechanisms to treat acute pain crises. RBC oxidative damage caused by continuous endogenous and exogenous oxidative stress may participate in the occurrence of vaso-occlusive crises. In this presentation, we will discuss how endogenous reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) can activate multiple kinases creating a positive feedback loop within sickle RBCs. We will provide in vitro and in vivo evidence supporting the RBC small non-coding nucleolar RNAs as messengers activated by this sickle cell vicious cycle to mediate endothelial adhesion. We will also discuss how disrupting this deleterious cycle can reduce not only vaso-occlusion in vivo, but sickle cell oxidative damage and inflammation as well.
Dr. Rahima Zennadi, associate-professor in the Division of Hematology at Duke University, has completed her PhD in Cancer Immunology from the University of Medicine in Nantes, France, and postdoctoral studies in Cancer Immunology from Duke University, USA. During the last decade, Her research shifted to working on sickle cell disease in the division of Hematology at Duke University, USA. She has published more than 25 manuscripts in peer-reviewed journals, and has served as an editorial board member. Dr. Zennadi was awarded funding from the National Institute of Health, foundations, and pharmaceutical companies. She is named inventor on three patents.
Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing neoplastic lymphocytes in the blood, marrow and secondary lymphoid tissues, resulting in lymphocytosis, leukaemia cell infiltration of the marrow, lymphadenopathy and splenomegaly. Several large genetic studies have revealed numerous genetic alterations in CLL, including single- nucleotide polymorphisms (SNPs), chromosomal alterations and alterations in non-coding RNAs, such as microRNAs (miRNAs), some of which can be used to determine prognosis and to guide management and therapeutic strategies as well. Different epigenetic changes like disordered methylation might enhance the evolutionary adaptive capacity of CLL cells by increasing the background â€˜noiseâ€™ of the genome, thereby providing increased opportunities for somatic mutations within the leukaemia clone. Interactions between CLL cells and their microenvironment, including interactions with other cell types, such as T cells, nurse-like cells and stromal cells, can induce B-cell proliferation and contribute to disease. All the molecules involved in these different types of pathogenic mechanisms of CLL can be included in a therapeutic model through the resort to ultra-low doses in the context of nanobiotechnologies, only able to allow the use of all of these molecules at the same time in order to avoid the resistance that is observed in conventional therapeutic approaches, even the most recent. We show a model of such a kind of nanotherapy called Bio Immune(G)ene Medicine and its clinical application in CLL as a biomimetic, holistic treatment without any side effects.
Gilbert Glady wav born in Strasbourg, France, Dr. Gilbert Glady graduated from Med School in 1977 and was then a resident in onco-hematology in the university clinic for several years. After a specialization in natural medicines in Paris, he returned to the Alsace region to work as a private practitioner. Through his work and encounters, he developed interest and expertise in immunology and immunogenetics, that leaded him to nanomedicine and nanobiotechnology. He thus became in 2010 the creator of the BI(G)MED method (Bio Immune(G)ene Medicine) and director of EBMA, the European association responsible for the communication and trainings in the field of BI(G)MED. He has participated in numerous international congresses in immuno-allergology, infectiology and oncology with posters and oral presentations, and is the author of several publications on nanobiotherapy in different journals.
The need of continuous quality assessment program for cell therapy manufacturing to maintain overall standards in assuring patient safety and drug and system efficacy through internal audits, validations, due diligence, strategic assessment, accreditations, certifications, clinical approvals and more, have changed the paradigms. QA ensures the demonstration of safety standards through implementation of safe controllable, consistent, GMP amenable manufacturing and drug delivery procedures. Maintaining standards for process assurance through implementing Standard Operating Procedures (SOP), Process Procedures (PP), Standard Testing Procedures (STP), Out Of Specifications (OOS), Corrective and Preventive Actions (CAPA). QA also need to conduct Management Review Meetings (MRM), vendor auditing and developing a system and procedures for process deviation management, risk management (failure mode effect analysis), archival systems, batch records, calibration records, manpower training and assessment, equipment and facility qualifications and logs etc. The main responsibility of QA is enforcing the cGMP standards, release of batches, monitoring the process for maintaining the cGMP compliances. Some of the errors or deviations in cell therapy manufacturing can be controlled through regular training, evaluations, and corrective actions to ensure the quality performances. Analyzing the notable events of deviations, manual errors, batch failures through developing a framework of developing online database and quarterly review will ensure deviation trends for process improvements, identifying recurring events etc. to minimize the potential risk and ensures the successful function of quality assurances. Here I am going to show you Quality Guidelines from three International Organizations: AABB (Advancing Transfusion and Cellular Therapies Worldwide), FACT (Foundation for the Accreditation of Cellular Therapy) and JACIE (The Joint Accreditation Committee ISCT-Europe & EBMT). All of them promote high-quality patient care and medical and laboratory practice through a profession-led, voluntary accreditation scheme.
Claudio Dario Dufour received a medical degree from the University of Buenos Aires, Argentina and completed his Internal Medicine Residency at the University of Buenos Aires Associated Bernardo Houssay Hospital of Vicente LÃ¯Â¿Â½pez, Buenos Aires. Dr. Dufour currently serves as Associate Professor of Medicine & Haematology at the Univ. of Buenos Aires, School of Medicine. Dr. Dufour holds membership in several professional societies: European Hematology Association (EHA), American Association of Blood Banks (AABB) and International Society of Cellular Therapy (ISCT). He has done a two Masters: Health Management at Dr. Favaloro s University, Argentina - 2010, and Stem Cell Transplantation at University of Valencia, Spain, 2015-2016. Dr. Dufour was elected as the 2014 winner at the Short Term Visiting Award of the EHA, scholarship where he developed skills in Stem cell Transplantation and Oncohematology. He is an active honorary collaborator at AABB, working as International Cell Therapy Ambassador for Latin America (2015 Ã¯Â¿Â½ 2018), and as Cell Therapy Assessor since 2012 up nowadays. He has done many trainees abroad in Stem Cell Transplantion: University of California (UCI) 1995; N. York Cord Blood Bank 2002, Barcelona Banc de Sang i Teixits 2005; LifeBank Vancouver, Canada 2011. Dr. Dufour has activities in Quality Management programs as ISO 9001 internal auditor for Bureau Veritas Argentina, and he has activities as Advisor in Cell Therapy in Argentina. His areas of interest include stem cell transplantation, cell therapies and regenerative medicine, multiple myeloma, the biology of plasma cells, new drug development, and special focus on pre & pos grade Educational Activities.
T cell Ig and ITIM domain (TIGIT), a member of Immune checkpoint family, is important in normal T-cell biology. However, the phenotypical profile and clinical relevance of TIGIT in follicular lymphoma (FL) is largely unknown. In the present study, using mass cytometry (CyTOF) to analyze a cohort of 82 FL patients, we showed that TIGIT was broadly expressed on intratumoral T cells and further analysis revealed that TIGIT was abundantly expressed on Treg, TFH, other CD4+ T cells and CD8+ T cells in FL. TIGIT-expressing T cells showed reduced cytokine production and poor proliferation and exhibited a distinct phenotypical profile when compared to TIGIT-negative T cells. In vitro assays revealed that TIGIT is co-induced with Foxp3 and is preferentially expressed on activated Treg cells (aTreg) which results in increased suppressive properties. Other TIGIT+ CD4+ T cells (residual CD4+ population) exhibit an exhaustion phenotype and are associated with an inferior patient survival. For CD8+ T cells, TIGIT was highly expressed on short-lived effector cells (SLECs) which also possess an exhaustion phenotype and are associated with a poor patient survival. In vitro assays confirm a role for lymphoma B cells in the maintenance of TIGIT expression on T cells. Overall, increased TIGIT+ T cells correlate with an inferior survival in FL and treatment with immunochemotherapy reverses this negative association. CITRUS analysis revealed that CD8+ cells mainly contribute to TIGIT-associated patient outcome. Taken together, the present study provides a comprehensive analysis of the phenotypic profile of intratumoral TIGIT+ T subsets and its prognostic relevance in FL. Inhibition of TIGIT signaling may be an additional mechanism to prevent T-cell suppression and exhaustion in B-cell NHL.
Zhi Zhang Yang, M.D., studies immune response in the tumor microenvironment of B-cell non-Hodgkin's lymphoma, a common cancer that usually involves lymph nodes and occasionally other tissues, These cells include T lymphocytes that seem to be more than simple residual elements from the normal lymph node structure.
Antiphospholipid syndrome (APS), may manifest itself as primary (PAPS) or secondary (SAPS). Repeated thromboses are the most frequent clinical manifestation of APS in the presence of antiphospholipid antibodies (aPL). APS patients suffer from various non-thrombotic manifestations, including thrombocitopenia. Methods: Our prospective study comprises of 468 patients: 318 with primary, 132 with secondary APS. Results:Thrombosis was diagnosed in 46.5% patients, with higher prevalence in PAPS compared to SAPS patients. There was similar prevalence of arterial thrombosis in PAPS and SAPS groups (34.6% and 34%, respectively, p=0.932) although venous thrombosis was more frequent in PAPS (25.9% and 8.5%, respectively, p=0.001). Thrombosis was observed in 92 (55.8%) patients who had more than one type of antibodies (category I), in 13 (41.9%) patients with category IIa, in 19 (46.3%) patients with category IIb, and in 73 (44.2%) patients with category IIc (p=0.10). The patients with thrombosis were older than those without thrombosis (49.8 and 39.8 years, respectively, p=0.001). Overall, older age was a risk factor for thrombosis. The prevalence of venous thrombosis was higher in the PAPS group, but with lower frequency than in literature data. Any aPL type and level is a risk factor for thrombosis. Thrombocytopenia more likely occurs in patients with both high aCL IgG and ÃŸ2GPI IgG levels. Keywords: antiphospholipid antibodies, antiphospholipid syndrome, thrombocytopenia. Funding:This work was supported by research grant number 175041 for 2011 â€“ 2020, and by research grant number TR 32040 for 2011-2020, issued by the Ministry of Science of the Republic of Serbia.
Ljudmila Stojanovich received her Ph.D. in Medicine in 1999. She is the scientific director in the Bezhanijska Kosa, University Medical Center of Belgrade University, where she is currently a Full Research Professor. She is an author of three monographs and of about 250 articles, published in international and domestic journals and in conference proceedings. She is in Editorial Boards (Editorial Boards LUPUS (LONDON). She is a member of number International Project, like of â€œthe European Forum on Antiphospholipid Antibodiesâ€. She was in Invited Speaker for many lectures in Congresses and Symposia; organizer and Chairman of many Seminars and Symposia; and member of the Steering Committee of the â€œEULAR recommendations for the prevention and management of adult antiphospholipid syndrome"
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in western countries and consists of a clinically heterogeneous group that exhibits similarities in morphology and immunophenotype. However, gene expression profiling (GEP) can further classify DLBCLs into distinct molecular subgroups based on cell-of-origin (COO), including germinal center B-cell type (GCB), activated B-cell type (ABC), or unclassified (UNC) type. COO assignment of DLBCL has important biological and prognostic significance, as well as potential therapeutic implications, with the ongoing development of selective agents for treatment of specific DLBCL subtypes. Here, we describe the use of a digital GEP assay (Lymph2Cx) to perform COO assignment in the routine work-up of DLBCL using formalin-fixed paraffin-embedded (FFPE) tissue sections and describe the results of 180 consecutive DLBCL cases analyzed prospectively by a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified clinical molecular diagnostics laboratory. We also describe the development of a new clinical GEP assay (Lymph3Cx) that can determine COO in DLBCL as well as robustly distinguish between DLBCL and primary mediastinal large B-cell lymphoma (PMBL). Large B-cell lymphoma cases analyzed so far include approximately 66% excisional biopsies, 33% needle core biopsies, and 1% cell blocks. Testing requires 2-4 unstained 10 micron tissue sections for all case types. Average turn-around-time for the assays is 2.3 business days in lab. This report describes the prospective application of the Lymph2Cx and Lymph3Cx assays in a clinical diagnostics laboratory and clearly illustrates how these assays can be incorporated into routine workflow for the workup of large B-cell lymphoma cases to determine COO as well as robustly distinguish between DLBCL and PMBL.
Dr. Ryan S. Robetorye received his M.D. and Ph.D. degrees from Baylor College of Medicine in Houston, Texas. He is board certified in Clinical Pathology, Hematology, and Molecular Genetic Pathology and currently works as a Consultant at the Mayo Clinic in Phoenix, Arizona. He currently serves as the Director of the Clinical Laboratories at the Mayo Clinic as well as the Medical Director of the Coagulation Laboratory, Co-Director of the Molecular Diagnostics Arizona Laboratory, and Medical Director of a Next-Generation Sequencing Laboratory. He is a current member of the College of American Pathologists Genomic Medicine Resource Committee and clinical laboratory Accreditation Committee. His research interests primarily involve hematological malignancies and molecular diagnostics involving gene expression profiling and next-generation sequencing.
Storage time for platelet concentrates is limited to five or seven days. Cryopreservation is considered a promising approach for extended platelet storage and bridging inventory shortages of conventionally liquid stored platelets in hospital practice as well as functioning as backup stock in crisis situations. In addition, extension of platelet storage time is critical for platelet availability in remote locations. Platelet freezing could also be used to build a phenotyped and/or genotyped platelet inventory to treat platelet refractory patients suffering from acute bleedings. Therefore, transfusion products of cryopreserved platelets (CPPs) in 5% dimethyl sulfoxide (DMSO) are currently in clinical development. So far, widespread clinical use of CPPs is presently restricted to military situations. Nevertheless, preservation of CPPsâ€™ functions and avoidance of transmission of infectious agents via CPPs remain challenges for a potential future introduction of CPPs into clinical use, and studies are needed to address these issues. In order to meet the challenge of transfusion transmitted pathogens, the INTERCEPT Blood System (Cerus Europe BV, Amersfoort, The Netherlands) uses a photochemical treatment (PCT) combining the psoralen derivate amotosalen and UVA light, which prevents pathogens and leukocytes from replicating and functioning. Because the use of PCT lowers the patient safety risks upon transfusion, their use as starting material for stocks of frozen platelets would be beneficial. Therefore, the objective of this study was, to analyze potential effects of the PCT on CPPs compared to untreated CPPs. Overall, our data show that cryopreserved platelets exert hemostatic potential in vitro, regardless of PCT-treatment or not.
Dr Per Sandgren PhD, senior researcher at the Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet Stockholm, Sweden works on factors involved in the initiation and counteracting of the platelet storage lesion. Effects of temperature, preparation, synthetic media and pathogen inactivation are, accordingly, of main interest. He is Chemist and Technical Manager at Department of Clinical Immunology and Transfusion Medicine (KITM), Karolinska University Hospital, Stockholm, Sweden. He has published more than 30 papers and 50 abstracts in reputed journals and has been serving as a member of thesis examination committees and referee for scientific journals of repute.
A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, personalized & precision medicine (PPM). To achieve the implementation of PPM concept, it is necessary to create a fundamentally new strategy based upon the subclinical and predictive recognition of biomarkers of hidden abnormalities long before the disease clinically manifests itself. Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks and from different periods of the individual life (including family planning and childhood to get the cancer risks minimized) for applications such as prediction and personalization of further canonical treatment and preventive-prophylactic manipulations to thus provide more tailored measures for the patients and persons-at-risk resulting in improved outcomes, reduced adverse events, and more cost effective use of health care resources. A lack of medical guidelines has been identified by the majority of responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PPM into daily practice of practitioners including oncologists of the next-step generations! PPM as being the Grand Challenge to forecast, to predict and to prevent is rooted in a big and a new science generated by the achievements of systems biology and translational Medicine (TM). NIH (Bethesda, USA) has included PPM into a List of The Greatest Priorities in XXI Century. Implementation of PPM requires a lot before the current model “physician-patient” could be gradually displaced by a new model “medical advisor-healthy person-at-risk”. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PPM to elicit the content of the new branch.
Sergey Suchkov was born in the City of Astrakhan, Russia, in a family of dynasty medical doctors. In 1980, graduated from Astrakhan State Med University and was awarded with MD. In 1985, maintained his PhD as a PhD student of the I.M. Sechenov Moscow Medical Academy and Inst of Med Enzymology. In 2001, maintained his Doctor Degree at the Nat Inst of Immunology, Russia. From 1989 through 1995, was being a Head of the Lab of Clin Immunology, Helmholtz Eye Research Inst in Moscow. From 1995 through 2004 - a Chair of the Dept for Clin Immunology, Moscow Clinical Research Institute (MONIKI). In 1993-1996, was a Secretary-in-Chief of the Edit Board, Biomedical Science, an int journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK. At present, Dr Sergey Suchkov, MD, PhD, is Professor, Director, Center for Personalized Medicine, Sechenov University and Dept of Clinical Immunology, A.I.Evdokimov Moscow State Medical and Dental University; Professor, Chair, Dept for Translational Medicine, Moscow Engineering Physical Institute (MEPhI), Russia; Secretary General, United Cultural Convention (UCC), Cambridge, UK. Dr Suchkov is a member of the New York Academy of Sciences, USA; American Chemical Society (ACS), USA
Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT) remains the treatment of choice to consolidate remission in patients with poor-pronostic oncohematology diseases. With increasing alternative donors available, the preferred donor or stem cell source is debated. The donor of choice for alloHSCT is a fully HLA matched sibling, which is available for only 20 to 25% of patients. Alternate donor sources have been developed and in the past few years transplant using these sources have surpassed the ones from sibling donor. These alternate sources are: adult volunteer donors which have been organized in large national registries; umbilical cord blood that is stored in blood banks worldwide; and manipulated stem cells grafts from haploidentical relatives. There is a wide variation in the transplant procedures, complications and outcomes between these sources, as well as debate over which one is the best source for each given patient, with few prospective comparative trials reported or in progress to settle this issue. We review the development and present status of each alternate source along with reported comparisons of properties and outcomes. The purposes of HSCT are: Rescue a cancer patient from the effects of high dose chemotherapy and total body radiation. The most common indications are leukemia and lymphomas, which account for more than two thirds of transplants, Correct a congenital or acquired cell disorder of the hematopoietic system (i.e., severe aplastic anemia and immune deficiencies, some inborn errors of metabolism); And control the proliferation of cancer cells through immune mediated mechanisms that from part of the graft versus host reaction. The goal of alloHSCT is to achieve adequate donor engraftment to reverse the hematology disease while minimizing Graft Versus Host Disease (GVHD) and late therapy-related effect. In summary substantial biases in donor selection are the result of center preference and it is not forthcoming that controlled clinical trials will be conducted to demonstrate superiority of one source above the other. On the other hand much work is being carried to improve the donor pool in all three donor sources: International registries continue to expand the chances for patients with uncommon HLA alleles to find a donor will improve steadily, especially for those from ethnic communities underrepresented in the registries; Work in expanding cord blood cells and understanding and manipulating their homing properties will result in safer transplantation of larger amounts of cells and faster hematopoietic reconstitution, And Groups developing haploidentical transplantation have worked hard in graft manipulation testing strategies of adding back alloreactive lymphocytes to reduce the risk of relapse while maintaining a low incidence of GVHD, and the goal to avoid other co-morbidites.
Claudio Dario Dufour received a medical degree from the University of Buenos Aires, Argentina and completed his Internal Medicine Residency at the University of Buenos Aires Associated Bernardo Houssay Hospital of Vicente Lï¿½pez, Buenos Aires. Dr. Dufour currently serves as Associate Professor of Medicine & Haematology at the Univ. of Buenos Aires, School of Medicine. Dr. Dufour holds membership in several professional societies: European Hematology Association (EHA), American Association of Blood Banks (AABB) and International Society of Cellular Therapy (ISCT). He has done a two Masters: Health Management at Dr. Favaloro s University, Argentina - 2010, and Stem Cell Transplantation at University of Valencia, Spain, 2015-2016. Dr. Dufour was elected as the 2014 winner at the Short Term Visiting Award of the EHA, scholarship where he developed skills in Stem cell Transplantation and Oncohematology. He is an active honorary collaborator at AABB, working as International Cell Therapy Ambassador for Latin America (2015 ï¿½ 2018), and as Cell Therapy Assessor since 2012 up nowadays. He has done many trainees abroad in Stem Cell Transplantion: University of California (UCI) 1995; N. York Cord Blood Bank 2002, Barcelona Banc de Sang i Teixits 2005; LifeBank Vancouver, Canada 2011. Dr. Dufour has activities in Quality Management programs as ISO 9001 internal auditor for Bureau Veritas Argentina, and he has activities as Advisor in Cell Therapy in Argentina. His areas of interest include stem cell transplantation, cell therapies and regenerative medicine, multiple myeloma, the biology of plasma cells, new drug development, and special focus on pre & pos grade Educational Activities.
MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs have been proposed as biomarkers of disease, including diagnosis, prognosis, and monitoring of treatment responses. These circulating miRNAs are highly stable in several body ï¬‚uids, including plasma and serum; hence, in view of their potential use as novel, non-invasive biomarkers, the proï¬les of circulating miRNAs have been explored in the ï¬eld of anti-doping. This lecture describes the enormous potential of circulating miRNAs as a new class of biomarkers for the detection of doping substances, and highlights the advantages of measuring these stable species over other methods that have already been implemented in anti-doping regimes. Incorporating longitudinal measurements of circulating miRNAs into the Athlete Biological Passport is proposed as an efï¬cient strategy for the implementation of these new biomarkers. Furthermore, potential challenges related to the transition of measurements of circulating miRNAs from research settings to practical anti-doping applications are presented. One of the major challenges in the anti-doping ï¬eld is the identiï¬cation of speciï¬c and sensitive non-invasive biomarkers that can be routinely measured in easily accessible samples. microRNAs (miRNAs) are a particularly promising class of biomarkers; these small (22 nucleotide), non-protein-encoding RNAs post- transcriptionally regulate gene expression via suppression of speciï¬c target mRNA. Furthermore, miRNAs have been shown to have a diagnostic or prognostic role and even potential clinical implications for targeted gene therapy in cancer patients.
Multivalent and multifunctional bioactive molecules offer the promise of more effective therapeutics. Herein, we present a new bispecific bio-agent â€œ MDF/SG 20â€ that modulate the interaction of leukocytes circulating in the blood vessels with the endothelial barrier cells and prevents the over flux of activated PMN to inflamed tissues. â€œMDF/SG 20â€ molecular design consisted in combining the CD11b A domain with the L selectin CD62, lectin-like domain in a single 52KDa fusion protein. We produced two structural recombinant forms, a linear and an IgG-like structure of â€œMDF/SG 20 in CHO cells. Both forms exhibited specific biological activity in real time of flow in physiological and inflammatory states using the ex vivo real-time imaging of leukocyte adhesion to the vascular endothelium of rats carotid arteries and HUVEC cell layers. Indeed, under inflammatory conditions, â€œMDF/SG 20â€ showed a significant inhibition of leukocytes tethering, rolling and adhesion to vascular endothelial cells. In addition, the transcription of IL6, ICAM1, VCAM1 and MCP1 gene and the expression of the corresponding proteins by respectively RT-PCR and immune fluorescence using specific Mabs, were significantly down regulated in endothelial cells treated with TNF and in presence of â€œMDF/SG 20â€. These observations delineates the underlying causes of the biological activity displayed by â€œMDF/SG 20â€. This work demonstrated that â€œMDF/SG 20â€ exerts inhibitory effects on human leukocytes interaction with vascular endothelium cells. This activity under flow in physiological and inflammatory conditions. The data provide strong mechanistic information about the anti-inflammatory properties of â€œMDF/SG 20â€ and are translatable into preclinical trial.
BACKGROUND: Central nervous system (CNS) relapse in patients with primary mediastinal large B-cell lymphoma (PMBCL) occurs in app. 6% of patients treated before Rituximab era and in 2% of patients receiving Rituximab-based chemotherapy. They usually occur shortly after the completion of chemotherapy. Potential risk factors for CNS relapse are elevated lactate dehydrogenase (LDH), young age and multifocal extranodal disease. METHODS: A retrospective analysis of 242 patients, with newly diagnosed PMBCL from 16 Polish hematooncology centers treated with rituximab based chemotherapy between 2003 and 2015 was performed. Patientsâ€™ characteristic: Consecutive patients aged 18 to 67 years (mean 33) including 147 women and 95 men received R-CHOP-21 (77), R-CHOP-14 (65), some responsive patients were consolidated with high dose chemotherapy and autologous hematopoietic stem cell transplantation and radiotherapy. 74 patients were treated with GMALL B-ALL/B-NHL 2002 protocol including high-dose methotrexate (MTX) 1.5 g/m2 and triple intrathecal (i.th.) prophylaxis. Patients treated with R-CHOP-21 and R-CHOP-14 received i.th. prophylaxis either with MTX or liposomal Ara-C at treating physicianâ€™s discretion. Clinical stage I and II disease was identified in 57.6% of patients. LDH was elevated in 83% of patients and bulky disease in 50,4%. Extranodal involvement of more than one site was identified in 16,9%, 17,1%, 24,4%, 19,5%, and 39% of patients in R-CHOP-21, R-CHOP, ASCT and GMALL groups respectively. Results: CNS relapse were noted in 2,9% of patients â€“ in 6% and in 3% of patients treated with R-CHOP-21 and R-CHOP-14 group respectively (one patient in second group received ith prophylaxis). Time to CNS relapse was very short: 1 to 2 months (mean 45 days). All patients were treated with HD-MTX and HD-Ara-C containing regimens and three of them were salvaged with high-dose chemotherapy and ASCT. One patient received cranial radiotherapy. 57% of patients died shortly after the diagnosis of lymphoma recurrence. Elevated LDH, ECOG 2 to 4, Ann Arbor stage III or IV and initially more than one extranodal site involved was revealed in 86%, 86%, 71%, and in 43% respectively. Higher mortality rate was observed in patients with no or only one extranodal localization. In 6 patients relapse was limited to the brain, in one patient as a part of systemic relapse. CONCLUSION: The prognosis of patient with CNS relapse of PMBCL is dismal. The recommendations for CNS relapse prevention are not established yet. In our study group no relapse was observed in patients treated with GMALL protocol, including both systemic high-dose MTX and intrathecal prophylaxis, which may suggest higher efficacy of this method over i.th treatment alone in prevention of CNS relapse, especially that most relapses occur in brain parenchyma. Further research should concentrate on identifying of prognostic factors for CNS relapse and on the need for CNS-oriented baseline staging as early isolated CNS relapse might be the sign of persisting occult CNS involvement .This should lead to optimization of CNS prophylaxis for patients at higher risk of relapse. The prognostic role of extranodal localization in disease progression requires further research. KEYWORDS: PMBCL; lymphoma; CNS relapse; CNS prophylaxis; Polish adult population
Eosinophilia has become one of the greatest diagnostic challenges in both hematology and general internal medicine. Sustained hypereosinophilia in peripheral blood (defined as absolute eoinophil count >1.5 x 109/L) encompasses both hematologic, as well as non-hematologic, conditions. As a matter of fact, clinicians face reactive, also known as secondary, causes of eosinophilia, much more frequently than hematopoietic disorders. Nevertheless, in a significant proportion of cases, reactive cause cannot be found; and, over time, end organ damage develops which necessitated diagnosis of hypereosinophilic syndrome. Broadly speaking, once secondary causes of eosinophila are ruled out, diagnostic considerations include WHO-defined myeloid and myeloid/lymphoid neoplasms, chronic eosinophilic leukemia, lymphocyte-variant hypereosinophilia, and hypereosinophilic syndrome. My presentation will focus on contemporary differential diagnostic algorithm which includes implementation of flow cytometry and molecular diagnostic techniques, including next generation sequencing approach. The latter has become particularly important since presence of certain molecular alterations makes patients eligible for targeted therapies with possibility of cure and stratifies them into distinct prognostic subgroups. Particular emphasis will be given on the up-to-date 2016 WHO classification of hematopoietic neoplasms and specific criteria and definitions of major types of eosinophilic disorders. Finally, novel approaches in patient management will be discussed.
Abstract: In the era of social media networking and cellphone applications, higher educators, have to adapt to external conditions to be up-to-date. Most applicable learning objectives should be introduced by user-friendly software or application to be used on demand and everywhere. Method: Approaches to anemia in childhood was selected for an innovative self-learning, self-evaluating software. The mobile application and social networking channel was introduced. Last year medical students (interns), General physicians, Pediatric residents and pediatricians were used this self-learning, self-evaluating software. External evaluation of this software and learning method was done by pre-test and post-test method and five-scale evaluation questionnaire by Education Development Office (EDO) of Shiraz Medical School. Results: Pre-test, post-test, and five-scale evaluation questionnaire from 100 pediatricians, 50 pediatric residents, 150 interns were done. Although the subject is essential for every physician and pediatrician, pre-test shows that 100% of the learners hadnâ€™t enough baseline knowledge of the subject. Post-test shows 95% of the learners successfully answered problem-solving, taxonomy III questions. All of the learners evaluated this self-learning, self-evaluating software as high quality, informative and user- friendly. Conclusion: faculty members have to commit to lifelong learning, adapting themselves with new technologies and must remember that professional role model to students is one of the main roles of the teachers; especially in the era of high technology mobile phones and social networking. This method of self-learning and self- evaluation of problem solving increases the ability of decision making in the absence of hazards for patients and ashamedness about mistakes. It is reasonably applicable for other subjects. Keywords: Education, Medical Students, Pediatric Residents, Self-learning, Self-evaluation. Background: : In the era of popular technologies such as social media networks and cellphone applications, higher education has to adapt to external conditions to be transformative and up-to-date . For faculty members especially medical teachers, must have the opportunity for concrete experiences capable of generating new methods of learning by using these devices. This paper will discuss an example of teaching an important part of Medical Students and Pediatric Residents' curriculum entitled: "approache to anemia in childhood". The paper will show what can be learned from this experience and a lifelong learning perspective which can help the higher education teachers. Every day many complete blood cell counts (CBC) is requested for patients with a wide variety of sign and symptoms. Unlike adults, in the field of Pediatric Hematology; there is wide variation in the normal range of hematological indexes including neonatal, early and late infancy, childhood and adolescent period. So, a given hemoglobin (Hb) or mean corpuscular volume (MCV) which is normal for cord blood and neonatal period is very high for other age groups. Medical students who will be the future doctors are studying in diverse Schools of Medicine, some of them may not have a Pediatric Hematologist-Oncologist to teach them this topic in detail. On the other hand, students and residents may not remember these values by a single traditional lecture. Even when they work in their offices they need to review this topic and refresh themselves. Method: Power point slides on the topic of Approach to anemia in childhood were prepared in detail (forty slides of traditional lectures were expanded to 140 slides). False positive and false negative results for lab tests were discussed by the presentation of cases, and after each chapter three question was asked to be interactive self-learning. An audio-video teaching file was created. Then multiple-choice questions with illustrations, images or lab data were prepared which had relevant feedbacks for every choice. The trainee had unlimited chance to try for answering until he/she reached the correct answer. At first, it was introduced by a computer-based self-learning on a DVD, then due to awareness of trainees' need a mobile application was designed to be more popular and flexible use of space and time; working outside the Hospital/ school; playful and game-based, with a higher degree of learners' autonomy. Then a social media channel was introduced for active discussion between the instructor of the software as manager of the channel, four fellowships of pediatric hematology as coordinators. New challenging questions were presented and participants were asked to reply their answers. The correct answer will be presented one day later. Effectiveness and quality of learning method was externally evaluated by EDO of Shiraz Medical School affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Results: This method was introduced and used by 100 Pediatricians in Fars Province Association of Pediatricians, 50 pediatric residents, and 150 Medical interns. Although the subject was necessary to know by every physician, pre-test was done before learning by 5 questions, but unfortunately 100% of the answers were wrong. Then they used the software and in post-test they successfully answered more than 95% of the complex, problem-solving, taxonomy III questions. Ninety-four percent of the trainees evaluated that interactive learning method and its content as high quality and effective. Table 1 shows details of the evaluation of the program by 100 pediatricians, 50 pediatric residents and 150 interns. Question 1: Is there enough explanation of the aims and purposes of the learning this subject at the presentation? Seventy-eight percent answered yes, 22% answered somehow. Question 2: is there association between aims and goals with the subject? Eighty-nine percent answered yes, 11% answered somehow. Question 3: is there association between your needs and the presented subject? Ninety-five percent answered yes, 5% answered somehow. Question 4: is the learning method interactive and informative? One-hundred percent answered yes. Question 5: is there enough time for thinking and answering to questions? Seventy-two percent answered yes, 28% answered more time is needed.