Physical Address

304 North Cardinal St.
Dorchester Center, MA 02124

Anemia of Chronic Inflammation

Anemia of chronic inflammation (ACI) is also termed anemia of chronic disease and considered the second most frequent anemia in the world, after iron deficiency anemia (IDA). ACI is also the most common anemia in hospitalized patients, found in conditions associated with an activated immune response, including chronic infections, autoimmune and inflammatory illnesses, and malignancy. The underlying cause of anemia in these diseases is multifactorial, including…

Disorders of Iron Homeostasis: Iron Deficiency and Overload

Iron is an essential nutrient for every cell of the body. Both decreased and increased total body iron, as well its inappropriate tissue distribution may be clinically important. In iron deficiency, limitation of the synthesis of physiologically active iron-containing compounds can have harmful consequences. In iron overload when iron exceeds the body’s capacity for safe transport and storage, iron toxicity may produce widespread cell (and organ)…

Iron Homeostasis and Its Disorders

Iron is an essential trace element required for energy production, oxygen transport and utilization, and cellular proliferation. Iron is a catalyst, acting as an electron donor and an electron acceptor by readily interconverting between ferric (Fe 3+ ) and ferrous (Fe 2+ ) forms. Iron functions mainly in association with proteins, either within prosthetic groups (heme, iron-sulfur clusters) or bound directly by amino acid side chains.…

Approach to Anemia in the Adult and Child

Anemia is the clinical state of red cell mass inappropriately low for the individual’s physiologic state. Anemias are among the most commonly encountered laboratory findings and clinical disorders in hematology. They encompass a broad range of clinical disorders and diseases with a spectrum of subtle to severe clinical impact on health. The approach to anemias can be direct if the cause is a common, singular or…

Pathobiology of the Human Erythrocyte and Its Hemoglobins

Anemia, polycythemia, and functional derangements of the human erythrocyte together represent a common group of human disorders with a significant impact on public health. Sickle cell disease, hemoglobin E (HbE)–associated disorders, and the thalassemias are humankind’s most common single-gene diseases, but the relevance of red blood cell (RBC) disorders to general medicine extends even beyond their individual clinical severities or the number of patients affected. A…

Acquired Disorders of Red Cell, White Cell, and Platelet Production

Acquired pure red cell aplasia (PRCA) is characterized by the presence of an acquired severe normochromic, most frequently normocytic anemia associated with a complete disappearance of reticulocytes and erythroid precursors in the marrow and normal production of myeloid cells and platelets. Consequently, it is presumed that the defect lies within erythroid precursors and not within stem cells as seen in aplastic anemia. Initially described as progressive…

Paroxysmal Nocturnal Hemoglobinuria

Introduction and History Paroxysmal nocturnal hemoglobinuria (PNH) is an opportunity to expound upon three major topics: hemolytic anemia, autoimmune-mediated bone marrow failure, and thrombosis. For the physician explaining a new diagnosis to the patient, PNH is now a cause for cautious optimism, as we have seen a tremendous improvement in the outcome over the past decades. Indeed, we can now alleviate symptoms and prevent complications in…

Aplastic Anemia

Aplastic anemia (AA), the paradigm of the bone marrow (BM) failure syndromes, is most simply defined as peripheral blood pancytopenia and a hypocellular BM ( Fig. 31.1 ). AA occurring as a primary hematologic disorder is historically denoted idiopathic, but it is now understood as immune-mediated. Constitutional marrow failure syndromes share a similar pathology of an apparently “empty” marrow (see Chapter 30 ) and can be…

Inherited Bone Marrow Failure Syndromes

Introduction Inherited bone marrow (BM) failure is defined herein as decreased production of one or more of the major hematopoietic lineages; i.e., red blood cells (RBCs), neutrophils, and platelets, due to germline mutations that were derived from the parents or occurred de novo ( Table 30.1 ). Although outdated, the term “constitutional” has been used interchangeably with “inherited” and similarly implies that a genetic abnormality causes…

Thrombocytopoiesis

Platelets, once regarded simply as ”blood dust,” are now recognized to play essential roles in hemostasis. Not only do they form a hemostatic plug and initiate thrombus formation in the event of vascular injury, but they also repair minute vascular damage that occurs on a daily basis. Platelets also participate in wound healing and angiogenesis via the delivery of key growth factors to sites of vascular…

Granulocytopoiesis and Monocytopoiesis

Granulocytopoiesis Granulocytes (neutrophils, eosinophils, and basophils) are short-lived cells that are critical to both antimicrobial and inflammatory responses. The bone marrow (BM) produces granulocytes, particularly neutrophils, at a prodigious rate to supply the baseline need for circulating cells that survive in the peripheral blood for only 3 to 24 hours. It also has the capacity to sharply increase granulocyte production in response to a wide range…

Biology Of Erythropoiesis, Erythroid Differentiation, And Maturation

The production of erythroid cells is a dynamic and exquisitely regulated process. The mature red cell is the final phase of a complex but orderly series of genetic events that is initiated when a multipotent stem cell commits to the erythroid program. Expression of the erythroid program occurs several divisions later in a greatly amplified population of erythroid cells, which have a characteristic form and structure,…

Treatment of Hematologic Malignancies With Genetically Modified T Cells

Conventional modalities for treating cancer remain unsatisfactory. Despite the introduction of small molecules that target specific molecular lesions or pathways within the cancer cells, cure rates for many common tumors remain low, while adverse events are still distressingly high. Cancer immunotherapy represents a promising extension of highly targeted cAncer therapy with potentially favorable toxicity and pharmacoeconomic profiles. Until recently, most attention has been on the development…

Unmodified Ex Vivo Expanded T Cells

T lymphocytes have the natural ability to destroy viral-infected or tumor target cells by a range of mechanisms that are initiated upon recognition of target peptides presented by histocompatibility antigens. Coupled with their ability to traffic through multiple tissues and self-renew, these properties make T lymphocytes an appealing cell-type for adoptive immunotherapy of cancer. Allogeneic hematopoietic stem cell transplantation (HSCT) is enduring “proof-of-principle” for adoptive immunotherapy…

T-Cell Immunity

Thymus-derived lymphocytes (T cells) play an essential role in the immune response to pathogens and against host cells that have undergone malignant transformation. T cells are critical regulators of the immune system that act through production of soluble mediators and direct interactions between ligands on the T-cell surface and receptors on other immune cells. This chapter reviews T-cell activation after engagement with specific antigens and describes…

Complement And Immunoglobulin Biology Leading To Clinical Translation

Complement and immunoglobulins represent the two major arms of humoral immunity and are discussed in detail in respective major subsections of this chapter. The complement section begins with a comprehensive overview of pathway activation, regulation, and effector mechanisms, followed by discussion of the pathological consequences of various complement deficiencies and polymorphisms. Next discussed is complement’s integral role in B-cell and T-cell immunity. Additional topics include the…

B-Cell Development

B lymphocytes are the subset of white blood cells specialized to synthesize and secrete immunoglobulin (Ig). Their name derives from the finding that the avian b ursa of Fabricius is a site of B-cell production. However, post-natal B-cell production in mammals takes place in the bone marrow. Following their production, newly generated B lymphocytes migrate into secondary lymphoid organs such as the spleen where they undergo…

Natural Killer Cell Immunity AND THERAPY

Natural killer (NK) cells are large, granular lymphocytes that comprise about 10% to 15% of the circulating peripheral blood lymphoctyes. These unique cells were first characterized by their ability to lyse targets independently of activating or initiating stimuli. NK cells are a critical cellular component of the innate immune system that have the ability to target and lyse malignant and virally infected cells. In addition, NK…

Dendritic Cell Biology

Dendritic cells (DCs), originally discovered in 1973 by Ralph M. Steinman and Zanvil A. Cohn and named after their distinct stellate morphology, are important regulators of immune responses. Specialized in antigen acquisition, processing, and presentation, the hallmark of DCs is their ability to induce naïve T cell activation and effector differentiation. DCs also interact with other immune cells, such as B cells, natural killer (NK) cells,…

Aging and Hematopoiesis

Aging Increase in life expectancy has resulted in a major demographic global shift toward an elderly population. As a consequence, the prevalence of a multitude of age-associated diseases has increased gradually during the last decades, resulting in an increased number of hospitalizations of elderly individuals. A better understanding of the mechanisms that cause aging is crucial in order to mitigate age-associated clinical conditions. Multiple “hallmarks” of…