| |
| |
| |
| Overview of Blood and Hematopoietic Tissues (Aster and Bunn) | |
| |
| |
| Impact of blood in health and disease | |
| |
| |
| Red blood cell | |
| |
| |
| White blood cells | |
| |
| |
| Platelets | |
| |
| |
| Blood clotting proteins | |
| |
| |
| The bone marrow | |
| |
| |
| The spleen | |
| |
| |
| The thymus | |
| |
| |
| Lymph nodes | |
| |
| |
| |
| Hematopoiesis and the Bone Marrow (Scadden) | |
| |
| |
| Hematopoietic cell diffrerentiation | |
| |
| |
| Myeloid lineage | |
| |
| |
| Erythroid lineage | |
| |
| |
| Megakaryocyte-platelet lineage | |
| |
| |
| Lymphoid lineages - B, T, and NK cells | |
| |
| |
| The biology of the stem cell | |
| |
| |
| Self-renewal | |
| |
| |
| Stem cell ontogeny | |
| |
| |
| Stem cell trafficking | |
| |
| |
| The regulation of blood cell formation | |
| |
| |
| The bone marrow niche and cell-cell interactions | |
| |
| |
| Cytokines in early hematopoietic differentiation | |
| |
| |
| Lineage specific cytokines | |
| |
| |
| Cytokine therapy | |
| |
| |
| Stem cell therapy | |
| |
| |
| |
| Anemias and Disorders of the Red Blood Cell | |
| |
| |
| |
| Overview of the Anemias (Bunn) (See full sample chapter) | |
| |
| |
| Definition of anemia | |
| |
| |
| Adaptations to anemia | |
| |
| |
| Alterations in blood flow | |
| |
| |
| Changes in oxygen unloading | |
| |
| |
| Stimulation of erythropoiesis | |
| |
| |
| Signs and symptoms of anemia | |
| |
| |
| Pathophysiology of anemia | |
| |
| |
| Anemia due to blood loss | |
| |
| |
| Anemia due to decreased red cell production | |
| |
| |
| Microcytic | |
| |
| |
| Macrocytic | |
| |
| |
| Normocytic | |
| |
| |
| Anemia due to increased red cell destruction | |
| |
| |
| |
| Anemias due to Bone Marrow Failure or Infiltration (Bunn) | |
| |
| |
| Congenital causes of bone marrow failure | |
| |
| |
| Acquired aplastic anemia and pure red cell aplasia | |
| |
| |
| Myelophthisis | |
| |
| |
| Myelodysplasia | |
| |
| |
| Leukemias (Myelodysplasia and the leukemias will be covered in detail in Chapters 21 and 22) | |
| |
| |
| |
| Iron Homeostasis: Deficiency and Overload (Heeney) | |
| |
| |
| Normal iron homeostasis | |
| |
| |
| Iron binding proteins: transferrin; ferritin | |
| |
| |
| The iron cycle | |
| |
| |
| Role of hepcidin in iron regulation | |
| |
| |
| Iron utilization in erythropoiesis | |
| |
| |
| Laboratory evaluation of iron status | |
| |
| |
| Serum iron and transferrin saturation | |
| |
| |
| Serum ferritin | |
| |
| |
| Bone marrow and liver iron stores | |
| |
| |
| Serum transferrin receptor | |
| |
| |
| Iron deficiency | |
| |
| |
| Etiology | |
| |
| |
| Clinical features - signs and symptoms | |
| |
| |
| Hematological features | |
| |
| |
| Treatment | |
| |
| |
| Iron overload | |
| |
| |
| Primary - inherited mutations in proteins regulating iron homeostasis | |
| |
| |
| Secondary - transfusional hemosiderosis | |
| |
| |
| |
| Megaloblastic Anemias (Heeney) | |
| |
| |
| Biochemistry of vitamin B12 and folate | |
| |
| |
| Pathophysiology | |
| |
| |
| Megaloblastic marrow and peripheral blood morphology | |
| |
| |
| Vitamin B12 and folate absorption | |
| |
| |
| B12 deficiency | |
| |
| |
| Etiology | |
| |
| |
| Clinical presentation (signs and symptoms) | |
| |
| |
| Laboratory evaluation | |
| |
| |
| Treatment | |
| |
| |
| Folate deficiency | |
| |
| |
| Etiology | |
| |
| |
| Clinical presentation (signs and symptoms) | |
| |
| |
| Laboratory evaluation | |
| |
| |
| Treatment | |
| |
| |
| |
| Anemias associated with Chronic Disease (Heeney and Bunn) | |
| |
| |
| Anemia of chronic inflammation | |
| |
| |
| Infection | |
| |
| |
| Cancer | |
| |
| |
| Connective tissue disorders | |
| |
| |
| Pathophysiology - role of hepcidin | |
| |
| |
| Lab features | |
| |
| |
| Treatment | |
| |
| |
| Anemia of renal insufficiency | |
| |
| |
| Cause | |
| |
| |
| Erythropoietin levels | |
| |
| |
| Treatment with erythropoietin and iron | |
| |
| |
| Anemia of chronic liver disease | |
| |
| |
| Anemia of endocrine hypofunction | |
| |
| |
| |
| Thalassemia (Nathan) | |
| |
| |
| Ontogeny of globin gene expression | |
| |
| |
| Organization of alpha and beta globin genes | |
| |
| |
| Definition and classification of the thalassemias | |
| |
| |
| Mutations responsible for the thalassemias | |
| |
| |
| Beta thalassemia | |
| |
| |
| Beta+ versus beta0 | |
| |
| |
| Beta thal major | |
| |
| |
| Cellular pathogenesis | |
| |
| |
| Clinical presentation | |
| |
| |
| Laboratory evaluation | |
| |
| |
| Complications | |
| |
| |
| Treatment | |
| |
| |
| Red cell transfusion | |
| |
| |
| Iron chelation | |
| |
| |
| Stem cell transplant | |
| |
| |
| Prevention - prenatal diagnosis | |
| |
| |
| Beta thal intermedia | |
| |
| |
| Beta thal minor | |
| |
| |
| Interacting beta thalassemias - Hb S and Hb E | |
| |
| |
| Alpha thalassemia | |
| |
| |
| Four degrees of gene deletion - correlate with clinical presentation | |
| |
| |
| Three alpha gene deletion - Hb H disease | |
| |
| |
| Four alpha gene deletion - Hydrops fetalis | |
| |
| |
| Prevention - prenatal diagnosis | |
| |
| |
| |
| Sickle Cell Disease and other Disorders of Hemoglobin Structure (Bunn) | |
| |
| |
| Inheritance - beta globin structural mutation: 6 Glu | |
| |
| |
| The sickling disorders: SS, S b 0 Thal, S b+Thal, SC, AS | |
| |
| |
| Molecular pathogenesis | |
| |
| |
| Structure of the sickle fiber | |
| |
| |
| Kinetics of fiber formation | |
| |
| |
| In vivo significance of polymer formation | |
| |
| |
| Cellular aspects of in vivo sickling and vaso-occlusion | |
| |
| |
| Contribution of Hb F | |
| |
| |
| Sickle cell - endothelial cell adhesion | |
| |
| |
| Clinical manifestations | |
| |
| |
| Constitutional: growth, development and susceptibility to infections | |
| |
| |
| Hemolytic anemia | |
| |
| |
| Vaso-occlusion | |
| |
| |
| Acute pain crises | |
| |
| |
| Acute chest syndrome | |
| |
| |
| Chronic organ damage | |
| |
| |
| Stroke | |
| |
| |
| Bone - aseptic necrosis | |
| |
| |
| Renal: impaired concentrating ability; impaired glomerular function | |
| |
| |
| Pulmonary hypertension | |
| |
| |
| Treatment | |
| |
| |
| Supportive - analgesia, oxygen, fluid and pH balance | |
| |
| |
| Prophylaxis: penicillin and vaccinations | |
| |
| |
| Hydroxyurea - induction of Hb F | |
| |
| |
| Novel therapeutic strategies | |
| |
| |
| |
| Other Inherited Hemolytic Anemias (Lux) | |
| |
| |
| Disorders of the red cell membrane | |
| |
| |
| Molecular anatomy of the red cell membrane | |
| |
| |
| Hereditary spherocytosis - mutations in spectrin, band 4.1, band 3 | |
| |
| |
| Other inherited membrane disorders | |
| |
| |
| Disorders of red cell metabolism | |
| |
| |
| Hexose monophosphate shunt and G6PD deficiency | |
| |
| |
| Glycolytic pathway - pyruvate kinase deficiency | |
| |
| |
| |
| Acquired Hemolytic Anemias (Bunn) | |
| |
| |
| Acquired membrane disorders | |
| |
| |
| Paroxysmal nocturnal hemoglobinuria | |
| |
| |
| Spur cell anemia | |
| |
| |
| Traumatic hemolytic disorders | |
| |
| |
| Thrombotic thrombocytopenic purpura (Covered in detail in Chapter 14) | |
| |
| |
| Hemolytic uremic syndrome | |
| |
| |
| Disseminated intravascular coagulation (Covered in detail in Chapter 16) | |
| |
| |
| Heart valve hemolysis | |
| |
| |
| Immune hemolytic anemias | |
| |
| |
| Pathophysiologic principles | |
| |
| |
| Clinical presentation and course | |
| |
| |
| Warm antibody hemolysis | |
| |
| |
| Cold antibody hemolysis | |
| |
| |
| Lab diagnosis | |
| |
| |
| Treatment | |
| |
| |
| |
| Erythrocytosis (Polycythemia) (Bunn) | |
| |
| |
| Pathophysiologic principles | |
| |
| |
| Algorithm for evaluating patients with erythrocytosis | |
| |
| |
| Primary erythrocytosis - polycythemia vera (See Chapter 20 for coverage of molecular pathogenesis, Chapter 22 for clinical presentation and course, diagnosis and treatment) | |
| |
| |
| Secondary erythrocytosis | |
| |
| |
| Appropriate erythropoietin production | |
| |
| |
| High altitude hypoxemia | |
| |
| |
| Pulmonary hypoxemia | |
| |
| |
| Cardiac hypoxemia (right to left shunt) | |
| |
| |
| Mutant hemoglobin with high oxygen affinity | |
| |
| |
| Inapproriate erythropoietin production | |
| |
| |
| Tumors: renal, hepatic | |
| |
| |
| Von Hippel Lindau syndrome | |
| |
| |
| Inherited disorders of oxygen sensing HIF pathway | |
| |
| |
| |
| Disorders of Hemostasis and Thrombosis | |
| |
| |
| |
| Overview of Hemostasis (Furie) | |
| |
| |
| Phases of clot formation and dissolution | |
| |
| |
| Platelet plug | |
| |
| |
| Coagulation | |
| |
| |
| Fibrinolysis | |
| |
| |
| Molecules that participate in clot formation and clot lysis | |
| |
| |
| Platelet activation | |
| |
| |
| Adhesion | |
| |
| |
| Aggregation | |
| |
| |
| Secretion | |
| |
| |
| Laboratory evaluation of platelet function | |
| |
| |
| Platelet aggregation | |
| |
| |
| Bleeding time | |
| |
| |
| Blood Coagulation | |
| |
| |
| In vitro coagulation cascade | |
| |
| |
| Laboratory evaluation | |
| |
| |
| Partial thromboplastin time | |
| |
| |
| Prothrombin time | |
| |
| |
| Thrombin time | |
| |
| |
| Fibrinogen | |
| |
| |
| Factor assays | |
| |
| |
| Factor VIII panel: activity, antigen, ristocetin cofactor, multimer assay | |
| |
| |
| D-dimer assay | |
| |
| |
| Mixing studies - identification of circulating anticoagulant | |
| |
| |
| Anticoagulent/fibrinolytic drugs | |
| |
| |
| Warfarin | |
| |
| |
| Heparin and heparin mimetics (see Chapter 17) | |
| |
| |
| Fibrinolytic agents | |
| |
| |
| |
| Platelet Disorders (Furie) | |
| |
| |
| Acquired Platelet Disorders | |
| |
| |
| Thrombocytopenia | |
| |
| |
| Decreased production | |
| |
| |
| Drugs, toxins | |
| |
| |
| Aplasia (Chap 4), myelodysplasia (Chap 22), PNH (Chap 11) | |
| |
| |
| Sequestration (hypersplenism) | |
| |
| |
| Increased consumption/destruction | |
| |
| |
| Immune thrombocytopenia | |
| |
| |
| Chronic ITP | |
| |
| |
| Acute ITP | |
| |
| |
| Drug induced | |
| |
| |
| Alloimmune | |
| |
| |
| Clinical presentation and course | |
| |
| |
| Treatment | |
| |
| |
| Thrombotic thrombocytopenic purpura | |
| |
| |
| Molecular pathogenesis | |
| |
| |
| Diagnostic criteria | |
| |
| |
| Clinical presentation and course | |
| |
| |
| Therapy | |
| |
| |
| Acquired qualitative platelet disorders | |
| |
| |
| Drug induced defects in platelet secretion: aspirin, NSAID | |
| |
| |
| Uremia | |
| |
| |
| Hereditary Platelet Disorders | |
| |
| |
| Defective adhesion: Bernard-Soulier | |
| |
| |
| Defects of release and of storage pools | |
| |
| |
| Defective aggregation: Glanzmann's thrombesthenia | |
| |
| |
| |
| Inherited Coagulation Disorders (Furie) | |
| |
| |
| Factor VIII deficiency (hemophilia A, classic hemophilia) | |
| |
| |
| Genetics x-linked mutations responsible for hemophilia A | |
| |
| |
| Clinical manifestions of disease | |
| |
| |
| Laboratory monitoring | |
| |
| |
| Therapy | |
| |
| |
| Factor VIII infusion | |
| |
| |
| Supportive care | |
| |
| |
| Complication of therapy | |
| |
| |
| HIV, viral hepatitis | |
| |
| |
| Acquired inhibitors (inducible and uninducible) | |
| |
| |
| Factor IX deficiency (hemophilia B, Christmas disease) | |
| |
| |
| Genetics x-linked mutations responsible for hemophilia B | |
| |
| |
| Clinical manifestions of disease | |
| |
| |
| Laboratory monitoring | |
| |
| |
| Therapy | |
| |
| |
| Factor IX concentrate infusion | |
| |
| |
| Supportive care | |
| |
| |
| Complication of therapy: HIV, viral hepatitis | |
| |
| |
| |
| Acquired Coagulation Disorders (Furie) | |
| |
| |
| Impaired synthesis of coagulation factors | |
| |
| |
| Liver disease | |
| |
| |
| Drugs | |
| |
| |
| Vitamin K deficiency | |
| |
| |
| Usual clinical setting | |
| |
| |
| Hemorrhagic disease of the newborn | |
| |
| |
| Factitious or accidental warfarin ingestion | |
| |
| |
| Disseminated intravascular coagulation | |
| |
| |
| Etiology | |
| |
| |
| Lab diagnosis | |
| |
| |
| Treatment | |
| |
| |
| Factor X deficiency and amyloid | |
| |
| |
| Coagulation factor deficiencies due to specific inhibitor | |
| |
| |
| Acquired Factor VIII deficiency | |
| |
| |
| Others: V, vWD, etc | |
| |
| |
| Lupus anticoagulant/anti-cariolipin (see Chapter 17) | |
| |
| |
| |
| Thrombotic Disorders (Bauer) | |
| |
| |
| Principles of thrombosis and thrombotic disorders | |
| |
| |
| Nation-wide and world-wide impact | |
| |
| |
| Virchow's triad | |
| |
| |
| Inhibitors/regulators of coagulation | |
| |
| |
| Anti-thrombin III - effect of heparin | |
| |
| |
| Protein S, activated protein C cleavage of Va and VIIIa | |
| |
| |
| Tissue factor protein inhibitor | |
| |
| |
| Fibrinolysis | |
| |
| |
| Risk factors for venous thrombosis | |
| |
| |
| Inherited thrombotic disorders | |
| |
| |
| Assay measurements | |
| |
| |
| Protein C deficiency - warfarin skin necrosis | |
| |
| |
| Protein S deficiency | |
| |
| |
| Factor V Leiden | |
| |
| |
| Prothrombin gene mutation: 20210 G-> A | |
| |
| |
| Impact of inherited defects on thrombotic risk | |
| |
| |
| Acquired thrombotic disorders | |
| |
| |
| Antiphospholipid antibody syndrome (lupus anticoagulant; anti-cardiolipin antibody) | |
| |
| |
| Clinical presentation | |
| |
| |
| Laboratory diagnosis | |
| |
| |
| Treatment | |
| |
| |
| Heparin-induced thrombocytopenia | |
| |
| |
| Pathogenetic mechanism | |
| |
| |
| Clinical presentation | |
| |
| |
| Laboratory diagnosis | |
| |
| |
| Treatment | |
| |
| |
| |
| Disorders of Leukocytes | |
| |
| |
| |
| Leukocyte Function and Non-malignant Leukocyte Disorders (Berliner) | |
| |
| |
| Distribution of cells within the myeloid/neutrophil compartment | |
| |
| |
| Marrow compartment | |
| |
| |
| Peripheral compartment | |
| |
| |
| Circulating | |
| |
| |
| Marginating | |
| |
| |
| Determinants of peripheral neutrophil count | |
| |
| |
| Production | |
| |
| |
| Margination | |
| |
| |
| Sequestration | |
| |
| |
| Destruction | |
| |
| |
| Evaluation of neutrophilia | |
| |
| |
| Primary hematologic disorders | |
| |
| |
| Congenital - e.g. Down's syndrome, inherited defects in leukocyte adhesion | |
| |
| |
| Acquired - e.g. chronic myeloid leukemia | |
| |
| |
| Secondary to other disorders | |
| |
| |
| Infection | |
| |
| |
| Stress | |
| |
| |
| Drug induces | |
| |
| |
| Chronic inflammation | |
| |
| |
| Post-splenectomy | |
| |
| |
| Approach to patient with neutrophilia | |
| |
| |
| Evaluation of neutropenia | |
| |
| |
| Congenital | |
| |
| |
| Constitutional, benign | |
| |
| |
| Severe congenital neutropenia | |
| |
| |
| Neutrophil elastase mutations | |
| |
| |
| Kostmann's syndrome | |
| |
| |
| Cyclic neutropenia | |
| |
| |
| Others | |
| |
| |
| Acquired neutropenia | |
| |
| |
| Post-infection | |
| |
| |
| Drug-induced | |
| |
| |
| Vitamin B12, folate deficiency | |
| |
| |
| Hypersplenism | |
| |
| |
| Immune related | |
| |
| |
| Auto-immune | |
| |
| |
| Isoimmune - newborns | |
| |
| |
| Associated with immune disorders | |
| |
| |
| Dignostic evaluation | |
| |
| |
| Treatment of neutropenias | |
| |
| |
| Depends on severity | |
| |
| |
| Wide range of options: supportive, steroids, IgG, G-CSF, stem cell transplant | |
| |
| |
| Qualitative abnormalities of neutrophil function | |
| |
| |
| Disorders of respiratory burst: chronic granulomatous disease, myeloperoxidase def | |
| |
| |
| Abnormalities of leukocyte adhesion and chemotaxis | |
| |
| |
| Defects in structure and function of neutrophil granules | |
| |
| |
| Non-malignant lymphocyte disorders | |
| |
| |
| Lymphocytosis | |
| |
| |
| Reactive lymphocytosis; cytomegalovirus, HIV, toxoplasmosis | |
| |
| |
| Infectious mononucleosis | |
| |
| |
| Lymphopenia: steroid therapy, immunodeficiency syndromes | |
| |
| |
| Histiocytic disorders - hemophagocytic lymphohistiocytosis | |
| |
| |
| |
| Introduction to Hematologic Malignancy (Fleming) | |
| |
| |
| Classes of hematologic malignancies | |
| |
| |
| Acute leukemias | |
| |
| |
| Myelodysplastic syndromes | |
| |
| |
| Chronic myeloproloferative disorders | |
| |
| |
| Lymphomas | |
| |
| |
| Diagnostic criteria | |
| |
| |
| Lineage of the malignant cell (cell of origin) | |
| |
| |
| Molecular genetic features | |
| |
| |
| Clinical features | |
| |
| |
| Clinical subtypes of disease | |
| |
| |
| Leukemia versus lymphoma | |
| |
| |
| Acute versus chronic leukemia | |
| |
| |
| Indolent versus aggressive lymphoma | |
| |
| |
| Clonality in hematologic malignancies | |
| |
| |
| Critical for distinguishing some neoplasms from reactive proliferations | |
| |
| |
| Established by a number of techniques | |
| |
| |
| X-chromosome inactivation (rarely used clinically) | |
| |
| |
| Conventional and molecular cytogenetics | |
| |
| |
| Acquired mutations of pathogenetic significance: e.g., JAK2 mutation in PCV | |
| |
| |
| B cells: production of monoclonal immunoglobulin protein | |
| |
| |
| B cells or T-cells: detection of monoclonal antigen receptor gene rearrangements | |
| |
| |
| |
| Molecular Mechanisms underlying Hematologic Malignancies (Aster) | |
| |
| |
| Chronic myeloproliferative disorders: tumors caused by mutations in tyrosine kinases | |
| |
| |
| Pathophysiology: hyperproliferation of hematopoietic progenitors with preserved differentiation | |
| |
| |
| Chronic myeloid leukemia: BCR-ABL fusion oncoproteins | |
| |
| |
| Polycythemia vera: gain of function JAK2 mutations | |
| |
| |
| Chronic eosinophilic leukemia: gain of function FGFR1 or PDGFR mutations | |
| |
| |
| Targeted therapies with kinase inhibitors | |
| |
| |
| Acute leukemias: tumors caused by complementary mutations in critical transcription factors and tyrosine kinases | |
| |
| |
| Pathophysiology: hyperproliferation of blasts and arrested development leading to bone marrow failure | |
| |
| |
| Acute promyelocytic leukemia | |
| |
| |
| Molecular pathogenesis: PML/RARa fusion proteins + tyrosine kinase mutations | |
| |
| |
| Targeted therapy - all-trans retinoic acid | |
| |
| |
| BCR-ABL+ acute lymphoblastic leukemia | |
| |
| |
| Molecular pathogenesis: Ikaros mutations + BCR-ABL fusion genes | |
| |
| |
| Targeted therapy - ABL kinase inhibitors | |
| |
| |
| Myelodysplasia | |
| |
| |
| Pathophysiology: acquired mutations that lead to apoptosis of hematopoietic progenitors (ineffective hematopoiesis) and disordered (dysplastic) maturation | |
| |
| |
| Genetic and cytogenetics | |
| |
| |
| Lymphomas: mainly tumors of mature lymphocytes | |
| |
| |
| Germinal center B cells - most common origin for human lymphomas | |
| |
| |
| Role of genomic instability in germinal center B cell lymphomas | |
| |
| |
| Recurrent genetic abnormalities: translocations involving BCL2, BCL6, and C-MYC | |
| |
| |
| Other contributors to B cell lymphomagenesis | |
| |
| |
| Chronic immune stimulation | |
| |
| |
| Chronic immune dysregulation | |
| |
| |
| Oncogenic viruses (EBV) | |
| |
| |
| T/NK cell lymphomas - rare, usually extranodal, diverse clinicopathologic features | |
| |
| |
| EBV-related (subset) | |
| |
| |
| ALK tyrosine kinase fusion protein-related (subset) | |
| |
| |
| Plasma cell neoplasms and related disorders | |
| |
| |
| Pathophysiology | |
| |
| |
| Abnormal immunoglobulins | |
| |
| |
| Bone resorption | |
| |
| |
| Suppression of B cell function | |
| |
| |
| Diminished hematopoiesis | |
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| Genetics: diverse chromosomal translocations involving the IgH locus | |
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| Acute Leukemias (DeAngelo) | |
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| Impact relative to cancer in general | |
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| Clinical presentation | |
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| Laboratory diagnosis | |
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| Blood and marrow morphology | |
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| Cell surface markers | |
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| Karyotype | |
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| Acute myeloid leukemia | |
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| Etiology | |
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| Principles of treatment | |
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| Induction | |
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| Post remission consolidation | |
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| Stem cell transplantation in selected patients | |
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| Factors influencing outcome | |
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| Age | |
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| Karyotype | |
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| WBC at presentation | |
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| Rapidity of response to induction therapy | |
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| Targeted therapy (APML and all-trans retinoic acid) | |
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| Acute lymphoblastic leukemia | |
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| Age-dependent incidence | |
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| Prognostic factors | |
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| Treatment | |
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| Induction | |
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| CNS prophylaxis | |
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| Consolidation | |
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| Maintenance | |
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| Treatment issues | |
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| Toxicity: myelosuppression, liver, CNS, pancreas | |
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| Infections | |
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| Complications of steroid therapy | |
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| Sites of relapse | |
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| Chronic lymphocytic leukemia | |
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| Clinical presentation | |
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| Staging | |
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| Prognostic factors | |
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| Treatment | |
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| Patients with early stage and/or minimal symptoms require no treatment | |
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| Chemotherapy | |
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| Anti-CD20 monoclonal antibody | |
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| The Myeloproliferative Disorders and Myelodysplasia (DeAngelo) | |
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| Clonal disorders arising from mutated hematopoietic stem cells | |
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| Chronic myeloid leukemia | |
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| Molecular pathogenesis: BCR-ABL fusion protein | |
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| Natural history | |
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| Laboratory diagnosis | |
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| Treatment | |
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| Targeted drug therapy: imatinib and newer tyrosine kinase inhibitors | |
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| Conventional chemotherapy | |
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| Stem cell transplantation | |
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| Polycythemia vera | |
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| Molecular pathogenesis: JAK2 kinase mutations | |
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| Clinical presentation and course | |
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| Laboratory diagnosis | |
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| Treatment: phlebotomy versus hydroxyurea | |
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| Essential Thrombocytosis | |
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| Molecular pathogenesis: majority of patients have JAK2 mutation | |
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| Clinical presentation and course | |
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| Laboratory diagnosis | |
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| Treatment | |
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| Primary myelofibrosis | |
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| Molecular pathogenesis: JAK2 mutations (50%), rarely MPL mutations | |
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| Clinical presentation and course | |
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| Laboratory diagnosis | |
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| Treatment | |
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| Myelodysplastic Syndromes | |
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| Clonal disorders arising from mutated myeloid stem cell | |
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| Morphologic feature: trilineage dysplasia | |
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| Clinical presentation | |
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| Elderly patient develops anemia, pancytopenia | |
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| Highly variable course | |
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| Classification - presence of blasts, cytogenetic abnormalities worsen outcome | |
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| Treatment - supportive, growth factors, chemotherapy, revlimid, stem cell transplant | |
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| Hodgkin Lymphoma, Non-Hodgkin Lymphoma and Plasma Cell Disorders (Freedman) | |
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| Introduction | |
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| Neoplastic transformation of normal lymphoid cells | |
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| Epidemiology | |
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| Approach to patient: evaluation, staging | |
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| Classification | |
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| Non-Hodgkin - indolent, aggressive, highly aggressive | |
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| Hodgkin - variable, usually moderately aggressive | |
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| Clinical presentation and course | |
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| Lymphadenopathy or extranodal mass | |
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| Diagnosis established by biopsy followed by staging | |
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| Treatment, clinical course and survival all depend on the precise diagnosis | |
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| Non-Hodgkin Lymphoma (NHL) | |
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| Indolent NHL | |
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| Usually follicular B cell lymphoma | |
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| Painless lymphadenopathy, extranodal sites uncommon | |
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| Survive for years without therapy | |
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| Not curable with current therapy | |
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| Treatment with radiation, chemotherapy and/or anti-CD20 indicated for | |
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| Bulky nodal disease | |
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| Compromised organ function | |
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| Symptomatic from fever and/or weight loss (B symptoms), effusions | |
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| Cytopenias | |
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| Aggressive NHL | |
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| Usually diffuse B cell | |
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| |
| Rapidly enlarging symptomatic masses | |
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| B symptoms | |
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| Extranodal sites common | |
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| |
| Transformation from indolent NHL | |
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| |
| High cure rate with chemotherapy + anti-CD20 | |
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| Hodgkin Lymphoma | |
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| |
| Clinical presentation: painless adenopathy; B symptoms in 30% | |
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| |
| Pathological classification | |
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| Orderly spread from one lymph node region to contiguous nodal sites | |
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| Importance of staging | |
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| Treatment | |
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| |
| Chemotherapy +/- radiation: 80% cured | |
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| Complications of therapy: cardiac, pulmonary, thyroid, second cancers | |
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| |
| Plasma Cell Disorders | |
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| |
| Clonal lymphoid cell proliferation producing structurally unique immunoglobulin | |
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| |
| Monoclonal gammopathy of uncertain significance (M-GUS) | |
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| |
| Often incidental finding in an elderly patient | |
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| |
| Converts to multiple myeloma at a rate of 1% per year | |
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| Multiple myeloma | |
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| |
| Malignant and progressive plasma cell proliferation associated with: anemia lytic bone lesions - due to activation of osteoclasts renal insufficiency - usually due to immunoglobulin light chain nephropathy acquired hypogammaglobulinemia leading to bacterial infections hypercalcemia | |
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| |
| Diagnosis serum electrophoresis -immunoglobulin M spike -associated hypogammaglobulinemia serum immunoelectrophoresis and immunofixation: IgG or IgA M spike urine immunoelectrophoresis: kappa or lambda light chains, bone marrow: increased plasma cells, often abnormal in appearance | |
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| |
| Treatment: chemotherapy, thalidomide, revlimid, proteasome inhibitors, stem cell transplant | |
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| |
| Waldenstroms Macroglobulinemia (Lymphoplasmacytic lymphoma) | |
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| |
| Malignant proliferation of lymphoplasmacytic cells producing IgM macroglobulins | |
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| |
| Associated with anemia, symptoms of plasma hyperviscosity | |
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| |
| |
| Transfusion Medicine | |
| |
| |
| |
| Blood Transfusion (Kaufman) | |
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| |
| Blood components | |
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| |
| Red cells | |
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| |
| Platelets | |
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| |
| Plasma | |
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| |
| Blood group antigens | |
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| ABO system | |
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| Structure of A, B and O antigens | |
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| |
| Immunological and clinical consequences | |
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| Rh system | |
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| Rh proteins | |
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| Rh antibodies - clinical consequences | |
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| |
| Other blood group antigens and antibodies | |
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| |
| Pretransfusion testing | |
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| |
| ABO typing | |
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| |
| Antibody screen | |
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| |
| Crossmatch | |
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| |
| Indications for transfusion | |
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| |
| Red cells | |
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| |
| Platelets | |
| |
| |
| Plasma | |
| |
| |
| Risks of transfusion | |
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| |
| Febrile reactions | |
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| |
| Hemolytic reactions acute delayed direct antiglobulin test | |
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| |
| Transfusion associated lung injury | |
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| |
| Transmission of infectious pathogens | |
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| |
| Viral: HIV, hepatitis | |
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| |
| Bacterial | |
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| |
| Hemolytic disease of the fetus and newborn | |
| |
| |
| Newer cellular therapies | |
| |
| |
| |
| Hematopoietic Stem Cell Transplantation (Antin) | |
| |
| |
| Transplantation immunology | |
| |
| |
| Major histocompatability antigens | |
| |
| |
| Minor histocompatability antigens | |
| |
| |
| Selection of donor | |
| |
| |
| Auto-transplant | |
| |
| |
| HLA-matched sibling donor | |
| |
| |
| Matched unrelated donor | |
| |
| |
| Source of donor stem cells | |
| |
| |
| Bone marrow | |
| |
| |
| Peripheral blood - isolated CD34+ cells | |
| |
| |
| Umbilical cord blood | |
| |
| |
| Preparation of recipient for stem cell transplant | |
| |
| |
| Minimal - aplastic anemia | |
| |
| |
| Full marrow ablation - necessary in hematologic malignancies | |
| |
| |
| Partial ablation - may prove beneficial in non-malignant disorders (SS) | |
| |
| |
| Clinical course and complications following transplant | |
| |
| |
| Infection | |
| |
| |
| Acute - bacterial | |
| |
| |
| Delayed - opportunistic | |
| |
| |
| Graft rejection | |
| |
| |
| Graft versus host disease / graft versus leukemia | |
| |
| |
| Impact of stem cell transplantation on | |
| |
| |
| Aplastic anemia | |
| |
| |
| Acute leukemias | |
| |
| |
| Chronic myelocytic leukemias | |
| |
| |
| Beta thalassemia major | |
| |
| |
| Sickle cell anemia | |
| |
| |
| Others Supplement: Tables of normal lab values | |
| |
| |
| Index | |