bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelodysplastic Syndromes
Authors: Greenberg Peter L. , Young Neal S. , Gattermann Norbert 
Published: August 2003

AbstractThe myelodysplastic syndromes (MDS) are characterized by hemopoietic insufficiency associated with cytopenias leading to serious morbidity plus the additional risk of leukemic transformation. Therapeutic dilemmas exist in MDS because of the disease’s multifactorial pathogenetic features, heterogeneous stages, and the patients’ generally elderly ages. Underlying the cytopenias and evolutionary potential in MDS are innate stem cell lesions, cellular/cytokine-mediated stromal defects, and immunologic derangements. This article reviews the developing understanding of biologic and molecular lesions in MDS and recently available biospecific drugs that are potentially capable of abrogating these abnormalities.Dr. Peter Greenberg’s discussion centers on decision-making approaches for these therapeutic options, considering the patient’s clinical factors and risk-based prognostic category.One mechanism underlying the marrow failure present in a portion of MDS patients is immunologic attack on the hemopoietic stem cells. Considerable overlap exists between aplastic anemia, paroxysmal nocturnal hemoglobinuria, and subsets of MDS. Common or intersecting pathophysiologic mechanisms appear to underlie hemopoietic cell destruction and genetic instability, which are characteristic of these diseases. Treatment results and new therapeutic strategies using immune modulation, as well as the role of the immune system in possible mechanisms responsible for genetic instability in MDS, will be the subject of discussion by Dr. Neal Young.A common morphological change found within MDS marrow cells, most sensitively demonstrated by electron microscopy, is the presence of ringed sideroblasts. Such assessment shows that this abnormal mitochondrial iron accumulation is not confined to the refractory anemia with ring sideroblast (RARS) subtype of MDS and may also contribute to numerous underlying MDS pathophysiological processes. Generation of abnormal sideroblast formation appears to be due to malfunction of the mitochondrial respiratory chain, attributable to mutations of mitochondrial DNA, to which aged individuals are most vulnerable. Such dysfunction leads to accumulation of toxic ferric iron in the mitochondrial matrix. Understanding the broad biologic consequences of these derangements is the focus of the discussion by Dr. Norbert Gattermann.
Acute Lymphoblastic Leukemia
Authors: Hoelzer Dieter , Gökbuget Nicola , Ottmann Oliver , Pui Ching-Hon , Relling Mary V. , Appelbaum Frederick R. , van Dongen Jacques J.M. , Szczepański Tomasz 
Published: August 2003

AbstractThis is a comprehensive overview on the most recent developments in diagnosis and treatment of acute lymphoblastic leukemia (ALL).Dr. Dieter Hoelzer and colleagues give an overview of current chemotherapy approaches, prognostic factors, risk stratification, and new treatment options such as tyrosine kinase inhibitors and monoclonal antibodies. Furthermore the role of minimal residual disease (MRD) for individual treatment decisions in prospective clinical studies in adult ALL is reviewed.Drs. Ching-Hon Pui and Mary Relling discuss late treatment sequelae in childhood ALL. The relation between the risk of second cancer and treatment schedule, pharmacogenetics, and gene expression profile studies is described. Also pathogenesis, risk factors, and management of other complications such as endocrinopathy, bone demineralization, obesity, and avascular necrosis of bone is reviewed.Dr. Fred Appelbaum addresses long-term results, late sequelae and quality of life in ALL patients after stem cell transplantation. New options for reduction of relapse risk, e.g., by intensified conditioning regimens or donor lymphocyte infusions, for reduction of mortality and new approaches such as nonmyeloablative transplantation in ALL are discussed.Drs. Jacques van Dongen and Tomasz Szczepanski demonstrate the prognostic value of MRD detection via flow cytometry or PCR analysis in childhood ALL. They discuss the relation between MRD results and type of treatment protocol, timing of the follow-up samples, and the applied technique and underline the importance of standardization and quality control. They also review MRD-based risk group definition and clinical consequences.
Chronic Lymphocytic Leukemia
Authors: Kay Neil E. , Hamblin Terry J. , Jelinek Diane F. , Dewald Gordon W. , Byrd John C. , Farag Sherif , Lucas Margaret , Lin Thomas 
Published: August 2003

Abstract
This update of early stage B-cell chronic lymphocytic leukemia (B-CLL) embraces current information on the diagnosis, biology, and intervention required to more fully develop algorithms for management of this disease. Emphasis on early stage is based on the rapid advancement in our understanding of the disease parameters and our increasing ability to predict for a given early stage patient whether there is a need for more aggressive management.
In Section I, Dr. Terry Hamblin addresses the nature of the disease, accurate diagnostic procedures, evidence for an early “preclinical” phase, the use of newer prognostic features to distinguish who will be likely to progress or not, and whether it is best to watch or treat early stage disease.
In Section II, Dr. Neil Kay and colleagues address the biologic aspects of the disease and how they may relate to disease progression. Review of the newer insights into gene expression, recurring genetic defects, role of cytokines/autocrine pathways, and the interaction of the CLL B cell with the microenvironment are emphasized. The relationship of these events to both trigger disease progression and as opportunities for future therapeutic intervention even in early stage disease is also considered.
In Section III, Dr. John Byrd and colleagues review the historical and now current approaches to management of the previously untreated progressive B-CLL patient. They discuss what decision tree could be used in the initial decision to treat a given patient. The use of single agents versus newer combination approaches such as chemoimmunotherapy are discussed here. In addition, the place of marrow transplant and some of the newer antibodies available for treatment of B-CLL are considered. Finally, a challenge to utilize our growing knowledge of the biology of B-CLL in the early stage B-CLL is proffered.
Multiple Myeloma
Authors: Anderson Kenneth C. , Shaughnessy John D. , Barlogie Bart , Harousseau Jean-Luc , Roodman G. David 
Published: August 2003

AbstractThis update provides new insights into the biology, diagnosis, prognosis, and treatment of multiple myeloma (MM) and its complications.In Section I, Drs. John Shaughnessy, Jr., and Bart Barlogie first correlate global gene microarray expression profiling of patient MM samples with normal plasma cells to provide the basis for a developmental stage-based classification of MM. The powerful clinical utility of these analyses is illustrated in delineating mechanism of drug action, identifying novel therapeutic targets, and providing a molecular analysis not only of the tumor cell, but also of the tumor microenvironment, in MM.In Section II, Dr. Jean-Luc Harousseau reviews the rationale and current results of high dose therapy and autologous stem cell transplantation in MM, including optimal patient selection, prognostic factors, conditioning regimens, sources of stem cells, use of tandem transplantation, and maintenance therapy. He then provides an update on the results of allotransplantation approaches in MM, focusing on proposed methods to reduce toxicity and exploit the graft-versus-MM alloimmune effect by transplantation earlier in the disease course, T cell depletion, and nonmyeloablative transplantation.In Section III, Dr. G. David Roodman provides recent insights into the mechanisms of osteoclast activation, interactions between bone and MM cells, adhesive interactions in MM bone disease, and osteoblast suppression. These recent advances not only provide insights into pathogenesis of MM bone disease, but also form the framework for novel therapeutics.In Section IV, Dr. Kenneth Anderson provides an up-to-date discussion of the role of the bone marrow microenvironment in promoting growth, survival, drug resistance, and migration of MM cells and the signaling cascades mediating these sequelae. These studies provide the framework for evaluation of novel therapeutics targeting the MM cell-host interaction in vivo in animal models and in derived clinical trials.
Lymphoma of the Skin
Authors: Connors Joseph M. , Hsi Eric D. , Foss Francine M. 
Published: August 2003

Abstract
This chapter describes the various ways in which the non-Hodgkin’s lymphomas can involve the skin, how these diseases should be assessed, standard treatments available in 2002, and new directions in research. The goal of the session is to succinctly review recent developments in lymphoma classification and treatment as they apply to the unique aspects of lymphoma when manifest in the skin.
In Section I, Dr. Eric Hsi reviews the special characteristics of the lymphomas seen when they proliferate in the skin and the application of the new World Health Organization classification system to the cutaneous lymphomas, emphasizing the unique challenges of recognizing and correctly classifying these diseases. He summarizes the evidence in favor of including the skin lymphomas in the overall lymphoma classification scheme and concludes with a practical description of the specific skin lymphoma entities.
In Section II, Dr. Joseph Connors describes the current optimal treatment of the B-cell lymphomas when they present in or metastasize to the skin. Building on the classification scheme described by Dr. Hsi, Dr. Connors outlines a treatment approach based on current understanding of pathophysiology of these diseases and application of each of the effective modalities available for cutaneous lymphoma including radiation, chemotherapy, and immunotherapy.
In Section III, Dr. Francine Foss concludes the session with a discussion of the different T-cell lymphomas that start in or spread to the skin concentrating on mycosis fungoides, cutaneous anaplastic large cell lymphoma and peripheral T-cell lymphoma. She includes comments on the newer anti-T-cell chemo- and immuno-therapeutics focusing on agents and techniques specific for cutaneous T-cell lymphomas.
Central Nervous System Lymphoma
Authors: Lister Andrew , Abrey Lauren E. , Sandlund John T. 
Published: August 2003

AbstractCentral nervous system involvement with malignant lymphoma whether primary or secondary is an uncommon but not rare complication observed in the management of patients with hematological malignancy. Its importance lies in the considerable morbidity and mortality with which it is associated and the inadequacy of therapy.In Section I, Dr. Lauren Abrey addresses the totality of the problem of primary central nervous system lymphoma, with emphasis on strategies increasingly dependent on systemic chemotherapy.In Section II, Dr. John Sandlund reviews the success of sequential clinical trials of overall therapy for acute lymphoblastic leukemia in childhood, identifying those patients at high risk of central nervous system leukemia and the development of a rational therapeutic strategy for prevention.In Section III, Dr. Andrew Lister discusses the issue of secondary central nervous system involvement with lymphoma and the indications for prophylaxis.
Atypical Cellular Disorders
Authors: Arceci Robert J. , Longley B. Jack , Emanuel Peter D. 
Published: August 2003

AbstractAtypical cellular disorders are commonly considered part of the gray zone linking oncology to hematology and immunology. Although these disorders are relatively uncommon, they often represent significant clinical problems, provide an opportunity to understand basic disease mechanisms, and serve as model systems for the development of novel targeted therapies. This chapter focuses on such disorders.In Section I, Dr. Arceci discusses the pathogenesis of Langerhans cell histiocytosis (LCH) in terms of the hypothesis that this disorder represents an atypical myeloproliferative syndrome. The clinical manifestations and treatment of LCH in children and adults is discussed along with possible future therapeutic approaches based upon biological considerations.In Section II, Dr. Longley considers the molecular changes in the c-Kit receptor that form the basis of mastocytosis. Based on the location and function of c-Kit mutations, he develops a paradigm for the development of specific, targeted therapies.In Section III, Dr. Emanuel provides a review of the “mixed myeloproliferative and myelodysplastic disorders,” including novel therapeutic approaches based on aberrant pathogenetic mechanisms. Taken together, these chapters should provide an overview of the biological basis for these disorders, their clinical manifestations, and new therapeutic approaches
Coagulation: Consultative Hemostasis
Authors: Hambleton Julie , Leung Lawrence L. , Levi Marcel 
Published: August 2003

AbstractClinical hematologists are frequently consulted for the care of hospitalized patients with complicated coagulopathies. This chapter provides an update on the scientific and clinical advances noted in disseminated intravascular coagulation (DIC) and discusses the challenges in hemostasis consultation.In Section I, Dr. Marcel Levi reviews advances in our understanding of the pathogenic mechanisms of DIC. Novel therapeutic strategies that have been developed and evaluated in patients with DIC are discussed, as are the clinical trials performed in patients with sepsis.In Section II, Dr. Lawrence Leung provides an overview of the challenging problems in thrombosis encountered in the inpatient setting. Patients with deep vein thrombosis that is refractory to conventional anticoagulation and those with extensive mesenteric thrombosis as well as the evaluation of a positive PF4/heparin ELISA in a post-operative setting are discussed. Novel treatments for recurrent catheter thrombosis in dialysis patients is addressed as well.In Section III, Dr. Julie Hambleton reviews the hemostatic complications of solid organ transplantation. Coagulopathy associated with liver transplantation, contribution of underlying thrombophilia to graft thrombosis, drug-induced microangiopathy, and the indication for postoperative prophylaxis are emphasized. Dr. Hambleton reviews the clinical trials evaluating hemostatic agents in patients undergoing liver transplantation.
Malaria and the Red Cell
Authors: Weatherall David J. , Miller Louis H. , Baruch Dror I. , Marsh Kevin , Doumbo Ogobara K. , Casals-Pascual Climent , Roberts David J. 
Published: August 2003

AbstractBecause of the breakdown of malaria control programs, the constant emergence of drug resistant parasites, and, possibly, climatic changes malaria poses a major problem for the developing countries. In addition, because of the speed of international travel it is being seen with increasing frequency as an imported disease in non-tropical countries. This update explores recent information about the pathophysiology of the disease, its protean hematological manifestations, and how carrier frequencies for the common hemoglobin disorders have been maintained by relative resistance to the malarial parasite.In Section I, Dr. Louis Miller and colleagues consider recent information about the pathophysiology of malarial infection, including new information about interactions between the malarial parasite and vascular endothelium.In Section II, Dr. David Roberts discusses what is known about the complex interactions between red cell production and destruction that characterize the anemia of malaria, one of the commonest causes of anemia in tropical countries.In Section III, Dr. David Weatherall reviews recent studies on how the high gene frequencies of the thalassemias and hemoglobin variants have been maintained by heterozygote advantage against malaria and how malaria has shaped the genetic structure of human populations.
Stem Cells: Hype and Reality
Authors: Verfaillie Catherine M. , Pera Martin F. , Lansdorp Peter M. 
Published: August 2003

AbstractThis update discusses what is known regarding embryonic and adult tissue-derived pluripotent stem cells, including the mechanisms underlying self-renewal without senescence, differentiation in multiple cell types both in vitro and in vivo, and future potential clinical uses of such stem cells.In Section I, Dr. Lansdorp reviews the structure and function of telomerase, the enzyme that restores telomeric ends of chromosomes upon cell division, highly present in embryonic stem cells but not adult stem cells. He discusses the structure and function of telomerase and signaling pathways activated by the enzyme, with special emphasis on normal and leukemic hematopoietic stem cells.In Section II, Dr. Pera reviews the present understanding of mammalian pluripotent embryonic stem cells. He discusses the concept of pluripotentiality in its embryonic context, derivation of stem cells from embryonic or fetal tissue, the basic properties of the stem cells, and methods to produce specific types of differentiated cell from stem cells. He examines the potential applications of stem cells in research and medicine and some of the barriers that must be crossed to achieve these goals.In Section III, Dr. Verfaillie reviews the present understanding of pluripotency of adult stem cells. She discusses the concept of stem cell plasticity, a term used to describe the greater potency described by several investigators of adult tissue-derived stem cells, critically reviews the published studies demonstrating stem cell plasticity, and possible mechanisms underlying such plasticity, and examines the possible role of pluripotent adult stem cells in research and medicine.
Non-Myeloablative Transplantation
Authors: Maloney David G. , Sandmaier Brenda M. , Mackinnon Stephen , Shizuru Judith A. 
Published: August 2003

AbstractThe concept of utilizing enhanced immunosuppression rather than myeloablative cytotoxic conditioning has allowed the engraftment of allogeneic stem cells from related and unrelated donors with lower early transplant-related mortality (TRM) and morbidity. This approach shifts tumor eradication to the graft-vs-host immune response directed against minor histocompatibility antigens expressed on tumor cells. This is not without risk, as the long-term effects of graft-versus-host disease (GVHD), it’s treatment, or resulting complications and immunodeficiency may be life threatening. However, this approach does allow the application of a potentially curative procedure to elderly or medically infirm patients who would not tolerate high-dose conditioning regimens.Section I, by Dr. Sandmaier, describes the current use of nonmyeloablative regimens and matched related or unrelated donors for the treatment of patients with CLL, CML, acute leukemia, MDS, lymphoma, and myeloma.In Section II, Dr. Maloney discusses the use of cytoreductive autologous followed by planned non-myeloablative allografts as treatment for patients with myeloma or NHL. This tandem transplant approach has a lower TRM than conventional high dose allografting. The nonmyeloablative allograft may allow the graft-versus-tumor (GVT) immune response to eradicate the minimal residual disease that causes nearly all patients with low-grade NHL or myeloma to relapse following autologous transplantation.In Section III, Dr. Mackinnon discusses the risks and benefits of T cell depletion strategies to prevent acute GVHD, while retaining GVT activity by planned donor lymphocyte infusions.Finally, in Section IV, Dr. Shizuru discusses the relationship between GVHD and GVT activity. Future studies, employing a greater understanding of these issues and the separation of GVHD from GVT activity by immunization or T cell cloning, may allow nonmyeloablative allogeneic transplantation to be safer and more effective.
Stem Cell Transplantation: Supportive Care and Long-Term Complications
Authors: Wingard John R. , Vogelsang Georgia B. , Deeg H. Joachim 
Published: August 2003

AbstractWith increasing hematopoietic stem cell transplant (HSCT) activity and improvement in outcomes, there are many thousands of HSCT survivors currently being followed by non-transplant clinicians for their healthcare. Several types of late sequelae from HSCT have been noted, and awareness of these complications is important in minimizing late morbidity and mortality. Late effects can include toxicities from the treatment regimen, infections from immunodeficiency, endocrine disturbances, growth impairment, psychosocial adjustment disorders, second malignancies, and chronic graft-versus-host disease (GVHD). A variety of risk factors for these complications have been noted. The clinician should be alert to the potential for these health issues. Preventive and treatment strategies can minimize morbidity from these problems and optimize outcomes.
Red Cell Antigens as Functional Molecules and Obstacles to Transfusion
Authors: Garratty George , Telen Marilyn J. , Petz Lawrence D. 
Published: August 2003

AbstractBlood group antigens (BGAs) can act as functional molecules but also can evoke autoantibodies and alloantibodies, causing autoimmune hemolytic anemia, hemolytic disease of the newborn and hemolytic transfusion reactions.In Section I, Dr. Marilyn Telen discusses physiologic and pathologic functions of RBC BGA-bearing molecules. She reviews some associations of BGAs with RBC membrane integrity and hemolytic anemia; association of BGAs with enzymatic and transport functions; and adhesion molecules expressed by RBCs, especially with reference to their pathophysiological role in sickle cell disease.In Section II, Dr. Lawrence Petz discusses the problems of providing blood for patients who have RBC autoantibodies. He provides an algorithm for excluding the presence of “hidden” alloantibodies, when all units appear to be incompatible due to the autoantibody. He emphasizes that clinicians should be aware of these approaches and not accept “the least incompatible unit.”In Section III, Dr. George Garratty describes two processes, in development, that produce RBCs that result in RBCs that can be described as “universal” donor or “stealth” RBCs. The first process involves changing group A, B, or AB RBCs into group O RBCs by removing the immunospecific sugars responsible for A and B specificity by using specific enzymes. The second process involves covering all BGAs on the RBC surface using polyethylene glycol (PEG). Results of in vitro and in vivo studies on these modified RBCs are discussed.
Enhancing Physician-Patient Communication
Authors: Lee Stephanie J. , Back Anthony L. , Block Susan D. , Stewart Susan K. 
Published: August 2003

AbstractPhysician-patient communication encompasses the verbal and nonverbal interactions that form the basis for the doctor-patient relationship. A growing body of research and guidelines development acknowledges that physicians do not have to be born with excellent communication skills, but rather can learn them as they practice the other aspects of medicine. Improvement in physician-patient communication can result in better patient care and help patients adapt to illness and treatment. In addition, knowledge of communication strategies may decrease stress on physicians because delivering bad news, dealing with patients’ emotions, and sharing decision making, particularly around issues of informed consent or when medical information is extremely complex, have been recognized by physicians as communication challenges. This paper will provide an overview of research aimed at improving patient outcome through better physician-patient communication and discuss guidelines and practical suggestions immediately applicable to clinical practice.