This succinct resource provides an ideal balance of the biology and practical therapeutic strategies for classic and non-classic BCR-ABL-negative myeloproliferative neoplasms. Utilizing current World Health Organization nomenclature, classification, and diagnostic criteria, international experts have assembled to convey the most up-to-date knowledge in this rapidly evolving field. The opening chapters cover the diagnosis and classification, genetics, cytogenetic findings, and prognostic factors of MPNs. Further chapters explore therapies specific to the different disease entities, including polycythemia vera, essential thrombocytopenia, myelofibrosis, and eosinophilic disorders, and mastocytosis. Unique areas of discussion include JAK2 inhibitor therapy, hematopoietic stem cell transplantation, and blastic transformation. A valuable reference for practicing hematologists, this forefront book enriches our understanding of recent discoveries and their impact on conventional and investigational treatments.

Hematopathology: Genomic Mechanisms of Neoplastic Diseases will keep physicians abreast of the rapid and complex changes in genomic medicine, as exemplified by the molecular pathology of hematologic malignancies. This timely volume will update physicians on the complexities of genomic lesions, as well as offer an integrated framework encompassing molecular diagnosis, the new WHO classification of hematologic neoplasms with focus on molecular pathology, prognostic value of molecular tests, and molecular monitoring of response to gene-targeted therapy. As such, it will be of great value to hematologists, oncologists, pathologists, internal medicine and pediatric specialists, as well as bioscientific staff and laboratorians in private hospitals and academic institutions.

Relapse of leukemia following successful remission-induction therapy remains a major obstacle in the treatment of patients with acute leukemia. Leukemia recurs most frequently in patients with acute myeloblastic leukemia (AML) and high risk acute lymphoblastic leukemia (ALL) following chemotherapy and less often in patients with low risk ALL and particularly in patient groups> submitted to allogeneic marrow transplantation. ' It is likely that the great majority of these recurrences originate from residual leukemic cells that survive initial remission-induction chemotherapy. Today, several research groups throughout the world place emphasis on studies concerned with the detection and treatment of 'minimal residual disease' (MRD). These investigations are conducted with the common objective to tackle the remaining cells. 'Minimal Residual Disease in Acute Leukemia: 1986' summarizes the fast advancements in this area. Several disciplines are concerned with the analysis of leukemic cells. The perspectives of cytogenetic and molecular genetic approaches for applica tion in the detection of MRD are reviewed. In this respect, modern cyto genetics provide highly specific tumor markers. The resolution of cyto genetic methods can be particularly improved when combined with other techniques which select relevant subpopulations of cells. Characterization of oncogenes and gene rearrangements, including those of immunoglobulin and T-cell receptor genes, and the measurement of gene products, have been established. Techniques based on these approaches offer interesting tools for the detection of MRD. New possibilities of employing monoclonal anti bodies are also presented.

The task the editors have set themselves is to survey the field of clinical hemorheology from basic principles to up-to-date research. It is only in a new science like this that it is possible to span the whole field in a book of this size. Hemorheology, as a new approach to the study and management of a wide range of circulatory diseases, is now beginning to appear with increasing frequency in general as well as specialized medical journals. Hemorheology is also just beginning to creep into the undergraduate medical curriculum. Therefore, the majority of graduate doctors are unequipped to assess the place of hemorheology in the overall framework of circulatory physiology and pathology or to assess its relevance to their everyday practice. It is hoped that this book will fill this gap. The approach of the book is interdisciplinary. The first part deals with basic principles of blood flow, circulation and hemorheology. It has been written with the general doctor in mind, who has no special knowledge of hemodynamics and rheological concepts, terminology or methodology. To maintain the emphasis on practical clinical applications, all the chapters in the second part of the book have been written by clinical specialists practicing in the individual areas of disease. The book is so designed that clinicians may be able to read the relevant chapters in the second part of the book in isolation, using the basic science aspects contained in the first part of the book as reference chapters.

A medical book need not be pretty, but it must be necessary and informative. This monograph on the clinical and diagnostic pathology of graft-versus-host disease, provid ing detailed visual information on the histo morphological and immunohistological fea tures of GvHD, is intended to close a gap in the otherwise comprehensive medical literature on GvHD. B. Heymer Acknowledgements No one accumulates knowledge alone. lowe thanks to: Prof. G. R. F. Kruger, Houston, for introducing me to the histomorphological analysis of GvHD Prof. R. Arnold, Berlin, for many fruitful clinico pathological discussions Prof. K. H. Muller-Hermelink, Wurzburg, for expert advice in difficult histological differential diagnoses Prof. W. Mohr, Ulm, for continuous support and encouragement in moments of fatigue Last, but by no means least, Mrs. R. Endres-Klein, Ulm, without whom the preparation of this book would have been impossible In addition, I am grateful to the editorial staff at Springer, Heidelberg. B. Heymer Contents 1 Introduction. . . . . . . . . . . . . 1 1. 1 What Is Graft-Versus-Host Disease? 1 1. 2 Has the Pathology of GvHD Changed in the Past Decades? . . . . 1 1. 3 Why Write a Synopsis of the Clinical and Diagnostic Pathology of GvHO? 2 2 Occurrence of GvHD . . . . . . . . . 5 2. 1 GvHD After Allogeneic Bone Marrow Transplantation . . . . . . . . . . . . . 6 2. 2 GvHD After Allogeneic Peripheral Blood Stem Cell Transplantation 6 2. 3 Alternative Donors . . . . . . . . . . . . 7 2. 4 Umbilical Cord Blood . . . . . . . . . . 7 2. 5 GvHD After Materno-fetal Transfusion 8 2. 6 GvHD After Blood Transfusion . . . . . 9 2."

The rates of acute leukemia cure have gradually improved over the last decade. Clinical study results reflect the impact of chemotherapy intensity and duration, the role of prolonged maintenance, intensified consolidation or very early intensification. Further progress has also been achieved in bone marrow trans plantation, and recent prospective studies and meta-analyses have contributed comparisons of the high antileukemic efficacy of bone marrow transplantation to that of improved chemotherapy. This allows a more successful combining of the two forms of treatment. New prognostic factors have emerged from both cytogenetic and molecular genetic research. Thus, the Philadelphia chromosome translocation and the bcr/abl gene rearrangement have proven to be the dominating risk factor in acute lymphoblastic leukemia. Since the frequency increases with age, differences in prognosis between children and adults can be explained. Evaluation of molecular and immunologic leukemia cell markers has provided a better understanding of residual leukemia in clinical remission, as a prognostic factor and in monitoring the effectiveness of the antileukemic strategy. Recent work on leukemic cell biology has resulted in novel therapeutic approaches such as terminal differentiation by all-trans-retinoic acid, modulation of chemotherapy by hematopoietic growth factors such as GM-CSF and enhancement of immunologic control by cytokines such as interleukin 2. New antimicrobial drugs and the application of mostly empiric anti-infectious strategies have helped reducing the therapeutic risk. Thus, a number of recent achievements have provided us with new options in the management of patients with acute leukemias."

Examination of the bone marrow has always been, and to-date techniques whose application will undoubtedly to a large extent still is, within the domain of the haema increase in the future. tologist. This is because smears of bone marrow aspirates After lengthy discussions and enquiries, the conclusion together with peripheral blood films and results of other was reached that the magnifications of most of the tests and investigations provided the information on which illustrations could be omitted without detracting from the usefulness of the Atlas. The magnifications used are the clinical diagnosis was based. Recently, the widespread availability of both improved indicated in Fig. 1.25. In addition, not every detail specif biopsy needles and techniques for processing has greatly ically indicated in a figure or its legend is necessarily increased the number of routinely taken bone biopsies mentioned in the text; and often a range of observations and placed the examination of bone marrow biopsy is illustrated and in these cases the legends are self sectiors also in the field of histopathology - so that explanatory. this Atlas is one of the Current Histopathology series. This Atlas is directed to haematologists and to histo Therefore, the haematologist and the histopathologist pathologists and to anyone interested in the investigation now complement each other in the interpretation of bone and understanding of the human bone marrow. marrow smears, imprints and sections, thus utilizing all available information and expertise to arrive at a diagnosis.

J. DE GROOTE One of the most ominous and troublesome complications of the liver disease is the appearance of hemorrhagic phenomena. Many careful clini- cal observations about the relationship of liver function and of bilia- ry tree pathology have been published. A vast amount of research work has been devoted to the subject. The severity of the hemorrhagic disor- der is usually in relation to the liver disease. In mild chronic hepa- titis or short lasting obstruction slight subcutaneous or mucosal blee- ding may (lraw the attention of the patient and the doctor, but they are as such far from dangerous. However in acute hepatic insufficiency, in biliary cirrhosis the bleeding tendency is to be considered as a life threatening complication in about half of the cases. Moreover coagulation disturbances aggravate bleeding not only from ruptured oesophageal or gastric varices but also from gastritis or peptic ulcer. 11enometrorrhagia, epistaxis and gingival bleeding may be very trouble- some in these conditions. The use of diagnostic procedures sucl. as liver puncture biopsy and peritoneoscopy are often impossible when platelets and prothrombine time are too low. In order to overcome this difficul- ty a procedure has been worked out taking a biopsy through a trans- jugular catheter placed in the hepatic vein. If a bleeding from the liver occurs it will be in the circulatory system and not cause any trouble.

International experts not only review the state-of-the-art in managing children and adults with acute leukemia, but also debate the pros and cons of current controversial and problematic issues. The book summarizes the best diagnostic and treatment practices for acute leukemias in children, adolescents, and adults. Among the therapies discussed are methotrexate, asparaginase, antipurines, epipodophyllotoxins, hematopoietic stem cell transplantation, hematopoietic growth factors, and immunotherapy.

Originally published in 1994, this readable and well-structured text opens with an overview of the concepts behind and advantages of blood stem cell transplants. Detailed concepts of their use are later expanded upon and critically reviewed by experts. Among the important issues discussed are hematopoietic recovery, tumor contamination and techniques used to purify stem cells. Clinical trial data follow including leukemia, lymphoma, myeloma and breast cancer. The final chapter evaluates progress in the use of blood stem cells and points possible clinical directions. This is a detailed review of the techniques in blood stem cell transplants which will be of value to anyone with an interest in the area.

A comprehensive and critical review of the latest scientific advances in our understanding of the molecular genetics and biology of CLL and their application to the best management of CLL. The authors focus on diagnosis, prognosis, multifaceted treatment options, and complications. Among the diverse treatments considered are chemotherapy, autologous and allogenic transplantations, monoclonal antibody therapy, immunotoxin therapy, gene therapy, and several new therapeutic strategies. Familial and juvenile chronic lymphocytic leukemia are also discussed.

Hemoglobin and Hemoglobinologists This volume, Hemoglobin Disorders: Molecular Methods and Protocols, will be introduced with a review of the great milestones in the field, and the scientists responsible for those achievements. The history of hemoglobin can be divided into three periods: the Classical period, the Modern period, and the Post-Modern period. I am inclined to include as the four major members of the classical period Francis Roughton, Quentin Gibson, Jeffries Wyman, and Linus Pauling, not only because of their achievements, but also because of the superb scientists they trained and/or influenced. Francis John Worsely Roughton (1899-1972) (Fig. 1), in his laboratory at Trinity College in Cambridge, England, made the first measurements of the rapid reaction of oxygen with hemoglobin at the millisecond scale, at first by flow-mixing methods and later by flash photolysis. He not only opened an era of molecular research of hemoglobin, but also invented the methodology for fast reactions through the use of laser technology, which was later improved by others so that even faster reactions could be detected. Another contribution of Roughton was the education of Quentin H. Gibson (Fig. 2), his favorite s- dent, who, in his laboratory in Sheffield, continued to expand the horizon of ligand binding to hemoglobin, defining the oxygen binding constants for each of the hemes of hemoglobin. Though this did not, as expected, solve the und- lying mechanism of ligand cooperativity as discussed below, it was nonet- less an important milestone.

Now in its second edition, Modern Hematology: Biology and Clinical Management reflects the major advances in the understanding, diagnosis, and treatment of blood disorders. It describes the latest clinical and scientific developments as well as details targeted and molecular therapies. The book brings together facts, concepts, and protocols important for the practice of hematology. In 23 chapters, all major blood diseases are covered, as well as rare diseases that are of scientific interest. As in the previous edition, each chapter is illustrated by tables, figures, and a selection of color plates.

High levels of homocysteine, a sulfur-containing amino acid derived from methionine, have recently been identified as a very important risk factor in cardiovascular disease. Homocysteine abnormalities are also thought to contribute to birth defects and dementia. There are many common genetic disorders and problems (such as vitamin deficiency) that adversely affect the metabolism of homocysteine. In this book a team of the world's experts in the field provide a clear, current, clinical analysis of the biochemistry, genetics, and epidemiology of homocysteine disorders, providing a uniquely comprehensive account of the broad range of medical, nutritional and methodological implications of homocysteine for health and disease.

This book aims to be a guide to the practice of blood conservation. The first chapter discusses the legal and administrative aspects of bloodless medicine describing the legal principles and practical issues relatd to refusal of transfusion. The second is on balancing the risks and benefits of transfusion includes clinical vignettes of appropriate and inappropriate transfusion. The remainder of the book covers the principles and practice of bloodless medicine, including a chapter on the scientific issues of haemostasis and the investigation of bleeding idsorders. The book concludes with chapters on blood conservation in neonatal and paediatric surgery, the costs associated with blood transfusion and the quest for artifical blood. New chapters will be included to address blood utilization in oncology and geriatric patients.

Myelodysplastic Syndromes was first published in 2006, and continues to stand out as the definitive text on the genetics, pathophysiology, and clinical management of this wide range of syndromes. It remains a major reference on all aspects of the clinical classification underlying pathogenetic mechanisms and treatment of the myelodysplastic syndromes. Authored by international experts, the book provides an assessment of the subject's status and a variety of advances in the field. The chapters cover all aspects of the myelodysplastic syndromes, from an in-depth analysis of the multifactorial nature of this disease, including a careful assessment of stromal, immunological and stem cell abnormalities, to a review of recent molecular and cytogenetic discoveries and insights. This book will be a valuable resource to clinicians and researchers who wish to learn more about myelodysplastic syndromes.

As a comprehensive reference on all aspects of the histiocytic disorders, Histiocytic Disorders of Children and Adults stands out a seminal text on the genetics, pathophysiology and clinical management of this wide range of diseases. The chapters, written by acknowledged experts in the field, cover all aspects of hystiocytic disorders, from Langerhans cell histiocytosis and hemophagocytic lymphohistiocytosis, to the uncommon cutaneous and extracutaneous histiocytic disorders. Views on the function of normal histiocytes in the immune system, the pathogenesis, underlying genetic defects, clinical presentation, treatment, controversies in therapy, salvage therapies and the late consequences are discussed in detail. Originally published in 2005, this book will be a valuable resource to clinicians and researchers who wish to learn more about histiocytic disorders.

In Leukemia and Lymphoma: Detection of Minimal Residual Disease, hands-on experts describe and discuss the minimal residual disease (MRD) methods they have successfully pioneered for leukemias and lymphomas. They apply reverse transcription PCR (RT-PCR) to acute myeloid leukemia (AML), chronic myelogenous leukemia (CML), and acute promyelocytic leukemia (APL). Other PCR methods are used for Non-Hodgkin's Lymphoma and for the monitoring of follicular lymphoma. Additional chapters address the use of real-time quantitative PCR (RQ-PCR), the emergent method of choice, in patients with acute lymphoblastic leukemia (ALL), the evaluation of MRD techniques in clinical trials, and the application of flow cytometry techniques.

The extravasation of cytotoxic agents can result in severe local tissue damage and medical emergencies during tumour therapy. This revised compendium is intended to help clinicians assess any situation speedily and with certainty. The general section of the book includes topics such as predisposition, prevention, type of harm, general measures in handling extravasated drugs, specific antidotes, and documentation. In the 2nd edition, the scientific information contained in the general section and relating to the actual substances has been updated. The substance specific part of the book includes detailed instructions on handling more than 50 cytotoxic drugs, to initiate targeted measures. Templates for an extravasation set, overview tables, documentation sheets, and patient information, as we as a CD-ROM are included to support clinical practice. The book is the outcome of a consensus of an interdisciplinary working group that has collected and systematically reviewed all published literature on the topic.

Face the hematology board certification with confidence! Hematology Rapid Review, created and edited by Drs. Utkarsh H. Acharya and Tejaswini Dhawale, is a conveniently portable and effective review tool that helps learners at all levels prepare for this challenging exam. Sturdy, full-colored, flash cards provide an efficient and focused review anytime, anywhere. Over 250 cards, 6" x 4", illustrated in full color. Card front asks either clinical case or case-independent high-yield questions. Card back provides the correct answer(s) and rationale. Expertly authored topics include ABIM Hematology Certification blueprint-based content covering a wide array of benign and malignant hematologic conditions. Enrich Your eBook Reading Experience Read directly on your preferred device(s), such as computer, tablet, or smartphone. Easily convert to audiobook, powering your content with natural language text-to-speech.

Anemia in the elderly has been properly defined as the silent epidemic, representing 3 million people in the United States aged 65 years and older. Incidence and prevalence of this condition increase with age. It differs in its etiology, pathogenesis and treatment from anemia in children and younger adults. Anemia is associated with reduced survival, increased risk of functional dependence and hospitalization, increased risk of congestive heart failure and stage renal disease and cognitive disorders. Approximately 70% of anemia in older individuals is reversible.

There are many haematological complications associated with obstetrics, pregnancy and gynaecology, and unfortunately, they often lead to significant morbidity or mortality for both mother and child. As the first comprehensive reference on all aspects of haematological complications of obstetrics, pregnancy and gynaecology this book will be a valuable resource to haematologists, obstetricians, gynaecologists, reproductive medicine specialists, internists, anaesthesiologists and others. The chapters are written by acknowledged experts in the field, and for each condition covered the etiology, pathophysiology, clinical and laboratory diagnosis and management are discussed where appropriate.

Due to major advances in understanding the biology and pathogenesis of the disease, the management of multiple myeloma is changing rapidly. New diagnostic and prognostic criteria have been introduced, and treatment options are multiplying with high-dose chemotherapy regimens, stem cell transplants, and the development of novel agents and immune-based strategies that target tumor cells directly. This book is aimed at the practitioner who is looking to put these advances into clinical context. It will serve as an up-to-date resource for treatment of myeloma and related disorders. Chapters are written by international authorities and contain color photos, diagrams, and algorithms outlining preferred treatment strategies. Relevant scientific information is integrated throughout, but the focus here is on providing practical therapeutic guidance for oncologists and hematologists caring for myeloma patients. The book covers all myeloma subtypes and related disorders, including amyloidosis, Waldenstrom macroglobulinemia, plasmacytoma, MGUS, and POEMS syndrome.

This book contains the contribution to the 37th Hemophilia Symposium, Hamburg 2006. The main topics are epidemiolgy, treatment of inhibitors in hemophiliacs, hemophilic arthropathy and synovitis, relevant hemophilia treatment 2006, and pediatric hemostasiology. The volume is rounded off by numerous free papers and posters on hemophilia, casuistics, and diagnostics.