SPEC – Lanzkowsky's Manual of Pediatric Hematology and Oncology, 7th Edition, 12-Month Access, EBook : SPEC – Lanzkowsky's Manual of Pediatric Hematology and Oncology, 7th Edition, 12-Month Access, EBook

__Lanzkowsky’s Manual of Pediatric Hematology and Oncology__, Seventh Edition remains the go-to clinical manual for the treatment and management of childhood cancers and blood disorders. It is a comprehensive book on patient management, replete with algorithms and flow diagrams, and includes a new section on vascular anomalies. Reflecting the considerable advances in the treatment and management of hematologic and oncologic diseases in children, the seventh edition of this successful clinical manual is entirely updated to incorporate all current treatment protocols, new drugs, and management approaches. Its concise and easy-to-read format, again, enables readers to make accurate diagnoses and treatment decisions without having to reference larger medical textbooks. Front Cover Lanzkowsky’s Manual of Pediatric Hematology and Oncology Copyright Page Dedication Contents List of contributors About the Editors Philip LanzkowskyFounding Author and Editor Jonathan D. Fish Managing Editor Jeffrey M. Lipton Preface to the seventh edition Preface to the sixth edition Preface to the fifth edition Preface to the fourth edition Preface to the third edition Preface to the second edition Preface to the first edition Introduction: Historic perspective (1955–2015) Reflection on 60 years of progress in pediatric hematology/oncology 1 Molecular and genomic methodologies for clinicians Clinical molecular and genomic methodologies: goals Methods of genetic analysis Markers of genetic defects Sequencing approaches Sanger sequencing Next-generation sequencing technologies and applications Interpretation of genetic variants obtained from next-generation sequencing Applications of next-generation sequencing to oncology Clinical interpretation of sequence variants in cancer Liquid tumor biopsies Epigenetic sequencing Single-cell sequencing Interpreting and evaluating the results from clinical genetic testing Further reading and references 2 Hematologic manifestations of systemic illness Alterations to red blood cells related to organ-specific pathologies Cardiovascular system Anemia Erythrocytosis Qualitative changes to RBC morphology Lungs Anemia Erythrocytosis Gastrointestinal tract Anemia Pancreas Anemia Liver Anemia Kidneys Anemia Endocrine system Anemia Erythrocytosis Skin Eczema and psoriasis Dermatitis herpetiformis Dyskeratosis congenita Alterations to white blood cells related to organ-specific pathologies Cardiovascular system Gastrointestinal tract Spleen Endocrine system Skin Mast cell disease Alterations to platelets and coagulation related to organ-specific pathologies Cardiovascular system Gastrointestinal tract Liver Thrombocytopenia Coagulation abnormalities Skin Ehlers–Danlos syndrome General considerations for the hematologic sequelae of infection Anemia White cell alterations Clotting abnormalities Thrombocytopenia Viral and bacterial illnesses associated with marked hematologic sequelae Parvovirus Epstein–Barr virus TORCHES infections Salmonella typhi Acute infectious lymphocytosis Bartonellosis Tuberculosis Leptospirosis (Weil disease) Severe acute respiratory syndrome coronavirus 2 Human immunodeficiency virus Thrombocytopenia Anemia and neutropenia Coagulation abnormalities Role of hematopoietic growth factors in treatment of AIDS-associated cytopenia Cancers in children with human immunodeficiency virus infection HIV-associated lymphoma Proliferative lesions of mucosa-associated lymphoid tissue Leiomyosarcomas and leiomyomas Kaposi sarcoma Leukemias Miscellaneous tumors Parasitic illnesses associated with marked hematologic sequelae Malaria Babesiosis Leishmaniasis Hookworm Tapeworm Trypanosomiasis Hemolytic uremic syndrome Autoimmune disease Rheumatoid arthritis Felty syndrome Systemic lupus erythematous Polyarteritis nodosa Wegener granulomatosis Kawasaki syndrome Henoch–Schönlein purpura Anemia of inflammation Inflammatory bowel disease as a model for anemia of inflammation Nutritional deficiencies and environmental exposures Protein–calorie malnutrition Scurvy Vitamin B12 deficiency Anorexia nervosa Lead intoxication Marrow infiltrative disorders Neoplastic disease Infantile malignant osteopetrosis (marble bone disease) Gaucher disease Niemann–Pick disease “Foam Cells” in bone marrow Cystinosis Further reading and references 3 Classification and diagnosis of anemia in children and neonates Classification and diagnosis Neonatal anemia Hemorrhage Prenatal blood loss Fetomaternal, intraplacental, and retroplacental hemorrhage Twin-to-twin transfusion syndrome Intrapartum blood loss Postnatal blood loss Clinical and laboratory findings of anemia due to hemorrhage Treatment Hemolysis Hemolytic anemia in the newborn Congenital erythrocyte defects Infantile pyknocytosis Hemoglobinopathies Gamma globin defects Beta globin defects Alpha chain defects Acquired erythrocyte defects Immune hemolytic anemia Rh isoimmunization Clinical features Laboratory findings Management Antenatal Postnatal Prevention of Rh hemolytic disease ABO isoimmunization Clinical features Diagnosis Treatment Late-onset anemia in immune hemolytic anemia Nonimmune hemolytic anemia Vitamin E deficiency Clinical findings Diagnosis Hypoplasia Congenital Acquired Viral diseases Anemia of prematurity Clinical features Treatment Physiologic anemia Diagnostic approach to anemia in the newborn Further reading and references 4 Nutritional anemias Overview Iron-deficiency anemia Introduction Prevalence Etiology Growth Diet Iron requirements of infancy Dietary iron content and requirements Menstrual blood loss Gastrointestinal blood loss and impaired absorption Iron-refractory iron-deficiency anemia Stages of iron depletion Nonhematological manifestations of iron deficiency Clinical features Differential diagnosis Laboratory parameters consistent with iron-deficiency anemia Treatment Correct underlying etiology Dietary counseling Infants and young children Dietary counseling: School-age children/adolescents Oral iron medication Intravenous iron therapy Indications Dose Formulations Side effects Contraindications to parenteral iron therapy Intramuscular iron Blood transfusion Summary Megaloblastic anemia Introduction Overview of vitamin B12 (cobalamin) absorption and metabolism Causes of vitamin B12 deficiency Inadequate intake/vitamin B12 nutritional deficiency Defective B12 absorption Gastric acidity and peptic activity deficiency Intrinsic factor deficiency Imerslund–Gräsbeck syndrome: Defective cobalamin transport by ileal enterocyte receptors for the intrinsic factor–cobalamin... Defective B12 transport Disorders of B12 metabolism Congenital Acquired Folic acid deficiency Overview of folate absorption and metabolism Causes of folate deficiency Inadequate intake/dietary folate deficiency Inborn errors of folate transport and metabolism Other megaloblastic anemias Clinical features of cobalamin and folate deficiency Diagnosis of cobalamin and folate deficiency Treatment Vitamin B12 deficiency Prevention Active treatment Response to vitamin B12 treatment Folic acid deficiency Treatment Response to folic acid treatment Further reading and references 5 Lymphadenopathy and diseases of the spleen Lymphadenopathy History Age Location Localized or generalized Size Character Diagnosis of lymphadenopathy Diseases of the spleen Asplenia Congenital polysplenia Accessory spleen Splenosis Sequestration of spleen Splenoptosis (splenic visceroptosis) Splenomegaly Diagnostic approach to splenomegaly Detailed history Physical examination Laboratory investigations Surgery involving the spleen Further reading and references 6 Bone marrow failure Aplastic anemia Acquired aplastic anemia Definition Pathophysiology Clinical manifestations Laboratory investigations Treatment Supportive care Hematopoietic stem cell transplantation Immunosuppressive therapy Antithymocyte globulin Cyclosporine Hematopoietic growth factors Treatment choices and long-term follow-up Salvage therapy Long-term sequelae and outcomes for SAA Treatment of moderate aplastic anemia Inherited bone marrow failure syndromes Fanconi anemia Pathophysiology and genetics Clinical manifestations Diagnosis Differential diagnosis Management Treatment Prognosis Dyskeratosis congenita Pathophysiology Genetics Clinical manifestations Treatment Congenital aplastic anemias of unknown inheritance Diamond Blackfan anemia Pathophysiology Genetics Clinical manifestations Diagnosis Differential diagnosis Treatment Prognosis Transient erythroblastopenia of childhood Pathophysiology Prognosis Treatment Congenital dyserythropoietic anemia Clinical manifestations Differential diagnosis Treatment Sideroblastic anemias (mitochondrial diseases with bone marrow failure syndromes) Laboratory findings Pathophysiology Treatment Severe congenital neutropenia and Kostmann syndrome Epidemiology Incidence Pathogenesis and genetics Clinical manifestations and laboratory Investigations Treatment Prognosis Reticular dysgenesis Treatment Shwachman Diamond syndrome SAMD9/9L-related syndromes Further reading and references 7 General considerations of hemolytic diseases, red cell membrane, and enzyme defects Clinical features of hemolytic disease Laboratory findings Accelerated hemoglobin catabolism Markers of extravascular hemolysis Markers of intravascular hemolysis Increased erythropoiesis Membrane defects Structure of the red cell membrane Red cell membrane disorders Hereditary spherocytosis Genetics Pathogenesis Hematologic features Biochemical features Clinical features Classification Diagnosis Complications Treatment Hereditary elliptocytosis Genetics Pathogenesis Hematologic features Clinical features Classification Treatment Hereditary pyropoikilocytosis Genetics Pathogenesis Biochemical and biophysical features Clinical features Differential diagnosis Treatment Hereditary stomatocytosis Definition and genetics Etiology Clinical features Overhydrated stomatocytosis Dehydrated stomatocytosis Differential diagnosis Treatment Hereditary acanthocytosis Definition Genetics Clinical features Diagnosis Differential diagnosis Paroxysmal nocturnal hemoglobinuria Pathogenesis Mechanism of hemolysis and hemoglobinuria in PNH Mechanism of hypercoagulable state Mechanism of defective hematopoiesis Clinical manifestations Course of the disease Complications Intravascular hemolysis (DAT negative) Venous thrombosis Defective hematopoiesis Infectious Other Diagnosis Management Hematopoietic stem cell transplantation Eculizumab Immunosuppressive therapy Use of hematopoietic growth factor Supportive therapy Enzyme defects PK deficiency Genetics Pathogenesis Hematology Clinical features Treatment Other enzyme deficiencies Glucose-6-phosphate dehydrogenase deficiency Genetics Pathogenesis Clinical features Drug-induced hemolysis Favism Neonatal jaundice Chronic nonspherocytic hemolytic anemia Treatment Other defects of glutathione metabolism Glutathione reductase Glutamylcysteine synthetase Glutathione synthetase Glutathione peroxidase Further reading and references 8 Extracorpuscular hemolytic anemia Immune hemolytic anemia Warm AIHA Clinical features Laboratory findings Initial management Blood transfusion Corticosteroid therapy Rituximab Intravenous gamma globulin Plasmapheresis Chronic management Immunomodulating agents Mycophenolate mofetil (MMF) Sirolimus Bortezomib Cyclosporine Danazol Azathioprine and 6-mercaptopurine (Antimetabolites) Cyclophosphamide (alkylating agent) Vincristine and vinblastine (mitotic inhibitors) Splenectomy Recombinant erythropoietin (rEPO) Hematopoietic stem cell transplant (HSCT) Giant cell hepatitis and DAT-positive AIHA Clinical findings Laboratory findings Treatment Cold AIHA Clinical features Treatment Paroxysmal cold hemoglobinuria due to Donath–Landsteiner cold hemolysin Clinical features Laboratory findings Differential diagnosis Treatment DAT-negative immune hemolytic anemia Nonimmune hemolytic anemia Microangiopathic hemolytic anemia Diagnosis Hypersplenism Wilson disease Further reading and references 9 Hemoglobinopathies Sickle cell disease Pathophysiology Incidence Genetics Prognosis Clinical features Hematology Acute complications Chronic complications and end-organ damage Prognosis Management Sickle cell trait (heterozygous form, AS) Pathophysiology Hematology Clinical features Significance Hemoglobin C Basic features and pathology HbC disease (homozygous CC) Hemoglobin E Unstable hemoglobins Thalassemias Basic features Main genetic variants β-Thalassemia: homozygous or compound heterozygous forms Pathogenesis Sequelae Hematology Biochemistry Clinical features Complications Causes of death Management Transfusion therapy Monitoring iron overload Chelation therapy Splenectomy Supportive care Pharmacologic enhancement of HbF synthesis Erythroid maturation agents Hematopoietic stem cell transplantation Gene therapy Management of the acutely ill patient with thalassemia Nontransfusion-dependent β-thalassemia (β-thalassemia intermedia) Clinical features Management β-Thalassemia minor or trait (heterozygous β0 or β+) α-Thalassemias Further reading and references 10 Primary and secondary erythrocytosis Erythrocytosis or polycythemia Primary erythrocytosis Polycythemia vera Pathophysiology Clinical features Diagnosis Treatment Primary familial and congenital erythrocytosis Secondary erythrocytosis Erythrocytosis in the newborn Symptoms Laboratory findings Treatment Congenital erythrocytosis due to altered hypoxia sensing Chuvash erythrocytosis and other von Hippel–Lindau mutations Hypoxia-inducible factor 2α mutations Prolyl hydroxylase domain-2 mutations High-affinity hemoglobinopathies 2,3-Bisphosphoglycerate deficiency Methemoglobinemia Other causes of erythrocytosis Diagnostic approach to erythrocytosis Further reading and references 11 Disorders of white blood cells Leukocytosis Leukopenia Neutrophil disorders Normal neutrophil development and function Neutrophilia Neutropenia Neutrophil dysfunction Approach to suspected neutrophil disorders Approach to neutrophilia Approach to neutropenia Approach to neutrophil dysfunction Primary neutrophilia disorders Hereditary neutrophilia Clinical presentation Diagnosis Management and treatment Primary neutropenia disorders ELANE–related neutropenia Clinical presentation Diagnosis Management and treatment Shwachman–Diamond syndrome (SDS) Clinical presentation Diagnosis Management and treatment Primary disorders of neutrophil dysfunction Warts, hypogammaglobulinemia, infections, and myelokathexis syndrome (WHIM) Clinical presentation Diagnosis Management and treatment Leukocyte adhesion defect, type 1 Clinical presentation Diagnosis Management and treatment Chediak–Higashi syndrome (CHS) Clinical presentation Diagnosis Management and treatment Chronic granulomatous disease Clinical presentation Diagnosis Management and treatment Secondary neutrophil disorders Secondary neutrophilia Secondary neutropenia Monocytes disorders Normal monocyte development and function Definition of monocytosis and monocytopenia Approach to suspected monocyte disorders Approach to monocytosis Approach to monocytopenia Primary monocyte disorders GATA2 haploinsufficiency Clinical manifestations Diagnosis Management and treatment options Secondary monocyte disorders Eosinophil disorders Normal eosinophil development and function Definition of eosinophilia and eosinopenia Approach to suspected eosinophil disorders Approach to eosinophilia Approach to eosinopenia Primary eosinophil disorders (M-HE/HES) Clinical manifestations Diagnosis Management and treatment options Secondary HE/HES Basophil disorders Normal basophil development and function Definition of basophilia and basopenia Approach to suspected basophil disorders Approach to basophilia Approach to basopenia Lymphocyte disorders Normal lymphocyte development and function T cells B cells NK cells Definition of lymphocytosis and lymphopenia Approach to lymphocytosis Primary lymphocytosis B-cell expansion with NF-(kappa)B and T-cell anergy syndrome Clinical manifestations Diagnosis Management and treatment Secondary lymphocytosis Approach to lymphocytopenia Primary lymphocytopenia disorders Severe combined immunodeficiency Clinical manifestations Diagnosis Management and treatment X-linked agammaglobulinemia Clinical manifestations Diagnosis Management and treatment NK-cell lymphopenia Secondary lymphocytopenia disorders Dedication Further reading and references 12 Disorders of platelets Thrombocytopenia in the newborn Neonatal alloimmune thrombocytopenia Pathophysiology Clinical features Diagnosis Treatment Management of subsequent pregnancies Neonatal autoimmune thrombocytopenia Pathophysiology Diagnosis Treatment General diagnostic approach to a newborn with thrombocytopenia Thrombocytopenia associated with hemolytic disease of the fetus and neonate Thrombocytopenia secondary to chronic fetal hypoxia, maternal diabetes, pregnancy-induced hypertension, or intrauterine gro... Thrombocytopenia secondary to congenital infections Late-onset thrombocytopenia secondary to late-onset infections, necrotizing enterocolitis, or thrombosis Thrombocytopenia due to aneuploidy Rare bone marrow disease or inborn errors of metabolism Metabolic causes Vascular anomalies Treatment Inherited thrombocytopenias Bernard–Soulier syndrome Treatment Gray platelet syndrome Myosin heavy chain 9 disorders Treatment Wiskott–Aldrich syndrome Pathophysiology Diagnosis Clinical manifestations Hematologic findings Treatment X-linked thrombocytopenia Anemia and thrombocytopenia with GATA1 mutation Paris–Trousseau syndrome/Jacobsen syndrome Thrombocytopenia with absent radii syndrome Treatment Congenital amegakaryocytic thrombocytopenia THPO-related thrombocytopenia Radioulnar synostosis with amegakaryocytic thrombocytopenia Familial platelet syndrome with predisposition to Acute Myelogenous Leukemia Inherited thrombocytopenia syndromes with predisposition to malignancies ANKRD26-related thrombocytopenia (familial thrombocytopenia type-2) ETV6-related thrombocytopenia Von Willebrand Disease Type 2B (VWDIIB) Miscellaneous diseases in which thrombocytopenia may be prominent but not the sole manifestation Immune thrombocytopenic purpura Pathophysiology Infections in immune thrombocytopenic purpura Clinical manifestations Diagnosis Treatment Supportive care Corticosteroids Intravenous Immuneglobulin (IVIG) Mechanism of action of intravenous immunoglobulin Adverse effects of intravenous immunoglobulin Anti-D therapy Mechanism of action Splenectomy Rituximab Dosage Mechanism of action Adverse effects Thrombopoietic receptor agonists Drugs that may be effective but are infrequently to rarely used in pediatric immune thrombocytopenic purpura Plasmapheresis Platelet transfusions Emergency therapy Chronic immune thrombocytopenic purpura Other causes of thrombocytopenia HIV-associated thrombocytopenia Drug-induced thrombocytopenia Heparin-induced thrombocytopenia Thrombotic microangiopathies Thrombotic thrombocytopenic purpura Clinical features Laboratory features Acquired thrombotic thrombocytopenic purpura Diagnostic evaluation Treatment Congenital thrombotic thrombocytopenic purpura (Upshaw–Shulman syndrome) Hemolytic–uremic syndrome Complement-mediated hemolytic-uremic syndrome Disseminated intravascular coagulation Autoimmune disorders Cyanotic congenital heart disease Hypersplenism Thrombocytosis Primary thrombocytosis Essential thrombocythemia Hereditary thrombocytosis Treatment of pediatric primary thrombocytosis Antiplatelet agents Cytoreductive therapy (platelet-lowering drugs) Qualitative platelet disorders Defects in platelet receptor–agonist interactions Selective impairments in platelet responsiveness to epinephrine Selective impairment in platelet responsiveness to collagen Defects in thromboxane A2 Selective impairment in platelet response to adenosine diphosphate Defects in platelet–vessel wall interaction Bernard–Soulier syndrome Type IIB von Willebrand disease and platelet-type (pseudo-von Willebrand) disease Defects in platelet–platelet interaction Glanzmann’s thrombasthenia Disorders of platelet secretion δ-Storage pool deficiency Hermansky–Pudlak syndrome Chédiak–Higashi syndrome α-Granule storage pool deficiency (gray platelet syndrome) Quebec platelet disorder (platelet factor V Quebec) Arthrogryposis–renal dysfunction–cholestasis Miscellaneous Impaired liberation of arachidonic acid pathways Cyclooxygenase and thromboxane synthetase deficiency Platelet intracellular signaling defects Kindlin-3 (leukocyte adhesion defect III) Dysregulated calcium signaling Deficiency of platelet procoagulant activity Scott syndrome Isolated defect in membrane vesiculation Acquired qualitative platelet disorders Medications Renal failure Liver disease Management of defects in platelet function Inherited vascular and connective tissue disorders Ehlers–Danlos syndrome Pseudoxanthoma elasticum Marfan’s syndrome Osteogenesis imperfecta Hereditary hemorrhagic telangiectasia Nonthrombocytopenic purpura Henoch–Schönlein purpura (anaphylactoid purpura) Infections Drugs Purpura factitia Gardner–Diamond syndrome Scurvy Laboratory evaluation of platelets and platelet function Examination of the blood smear Bleeding time Closure time Platelet aggregation in platelet-rich plasma Platelet aggregation in whole blood Further reading and references 13 Disorders of coagulation Hemostatic disorders Physiology of hemostasis Primary hemostatic mechanism (platelet phase) Platelet vessel interaction Fibrinolysis Natural inhibitors of coagulation Hemostasis in the newborn Plasma factors Blood vessels Platelets Approach to a bleeding child Initial screening tests Common confirmatory coagulation assays Global hemostatic tests Preoperative evaluation of hemostasis Acquired coagulation factor disorders Vitamin K deficiency Hepatic dysfunction Disseminated intravascular coagulation Inherited coagulation factor disorders Hemophilia A and B Genetics Clinical course of hemophilia Managing newborns with known or suspected hemophilia Treatment (factor replacement therapy) Ancillary therapy Antifibrinolytic therapy Management of inhibitors in hemophilia Low responders High responders Treatment of factor IX inhibitors Acquired hemophilia A Acquired antibodies to other coagulation factors Von Willebrand disease Diagnosis and treatment of vWD Type 1 vWD Type 2A vWD Type 2B vWD Type 2N vWD Type 2M vWD Type 3 vWD Platelet-type (pseudo-vWD) vWD Factor replacement for vWD Acquired vWD Rare coagulation factor disorders (FII, V, VII, X, XI, XIII, fibrinogen deficiencies) Thrombotic disorders Venous thrombosis Arterial thrombosis Hereditary thrombotic disorders Mechanisms of thrombosis in inherited thrombophilia Factor V Leiden (activated PC resistance) Prothrombin G20210A mutation (FII G20210A) Antithrombin deficiency Protein C deficiency Protein S deficiency Dysfibrinogenemia Prophylaxis in relatives of patients with thrombophilia Specific risk factors for venous thrombosis Acquired thrombotic disorders Antiphospholipid antibody syndrome Risk factors for thrombosis recurrence Indefinite anticoagulation Morbidity Thrombotic disorders arising in special conditions Antithrombotic therapy Heparin therapy Heparin antidote Low-molecular-weight heparin Dose (enoxaparin) (Lovenox, Aventis) Monitoring of LMWH therapy Adjusting LMWH dose Antidote for LMWH Heparin-induced thrombocytopenia (HIT) Factor Xa inhibitors Fondaparinux Rivaroxaban Apixaban Direct thrombin inhibitors Argatroban Bivalirudin Warfarin Antiplatelet therapy Aspirin Dipyridamole Clopidogrel Abciximab Thrombolytic therapy Tissue plasminogen activator Monitoring response of thrombolytic therapy Complications of thrombolytic therapy Further reading and references 14 Vascular anomalies Introduction Vascular tumors Benign vascular tumors Infantile and congenital hemangiomas Locally aggressive and borderline vascular tumors Kaposiform hemangioendothelioma Malignant vascular tumors Angiosarcoma Epithelioid hemangioendothelioma Simple vascular malformations Capillary malformations Venous malformations Lymphatic malformations Arteriovenous malformations Diagnostic work-up for vascular lesions History Physical examination Color Ecchymosis/bleeding/leaking Consistency Bruit Laboratory evaluations Imaging Management Key points Evaluation and monitoring of a vascular hepatic tumor Vascular anomaly syndromes Overgrowth syndromes Complex lymphatic anomalies Further reading and references 15 Histiocytic disorders Introduction Langerhans cell histiocytosis Incidence Pathology Pathogenesis Clinical features Involvement by site of disease Skeleton Skin Lungs Liver Hematopoietic system Lymph nodes Endocrine system Gastrointestinal system Central nervous system Hypothalamic pituitary involvement Laboratory studies for the diagnosis of DI Space-occupying central nervous system lesions Neurodegenerative disease Clinical and laboratory evaluation of Langerhans cell histiocytosis Diagnostic evaluation Laboratory testing Routine blood and serum tests Urine testing Radiographic studies Diagnostic biopsy Special situations Evaluating response to therapy Treatment of Langerhans cell histiocytosis Specific site Solitary bone lesions Localized skin involvement Solitary lymph node Multisystem disease Recurrent or refractory disease Prognosis Sequelae and complications Long-term complications Other histiocytic disorders Juvenile xanthogranuloma Erdheim–Chester disease Sinus histiocytosis with massive lymphadenopathy (Rosai–Dorfman disease) Malignant histiocytic disorders in children Treatment/outcome Localized disease Disseminated/multisystem disease Recurrent/refractory disease Hemophagocytic lymphohistiocytosis (hemophagocytic syndromes) Familial or primary hemophagocytic lymphohistiocytosis Pathophysiology, immunology, and genetics Clinical features Treatment Nonfamilial hemophagocytic lymphohistiocytosis Infection-associated hemophagocytic lymphohistiocytosis Treatment Malignancy-associated hemophagocytic syndrome Treatment Macrophage activation syndrome in systemic juvenile rheumatoid arthritis and other chronic conditions (reactive HLH) Treatment Further reading and references 16 Lymphoproliferative disorders Angioimmunoblastic lymphadenopathy with dysproteinemia Diagnosis Prognosis Treatment of AILD-type lymphoma Small lymphocytic infiltrates of the orbit and conjunctiva (ocular adnexal lymphoid proliferation, pseudolymphoma, benign l... Angiocentric immunolymphoproliferative disorders Clinical features Lymphomatoid granulomatosis Midline lethal granuloma Postmalignancy angiocentric immunolymphoproliferative lymphoma Treatment Castleman disease (angiofollicular lymph node hyperplasia, benign giant lymph node hyperplasia, angiomatous lymphoid hamartoma) Clinical features Unicentric hyaline vascular variant Unicentric plasma cell variant Multicentric plasma cell variant TAFRO variant Prognosis Localized disease Multicentric disease Treatment Localized disease Multicentric disease Epstein–Barr virus-associated Lymphoproliferative disorders in immunocompromised individuals Epstein–Barr virus antigens associated with the lytic cycle Cellular responses in the control of Epstein–Barr virus infection Reasons for persistence of latency in Epstein–Barr virus infection Inherited non Epstein–Barr virus-specific immunodeficiencies Inherited Epstein–Barr virus-specific immunodeficiencies Biological factors of significance involved in the pathogenesis of Lymphoproliferative disorders in this population Iatrogenically induced immunodeficiencies Organ transplantation recipients Hematopoietic stem cell transplantation recipients Diagnosis of PT-Lymphoproliferative disorders Treatment Treatment of B-cell lymphoproliferative disease in immunosuppressed patients General treatment Additional treatment considerations X-linked lymphoproliferative syndrome Pathophysiology Clinical manifestations Laboratory manifestations Treatment Prognosis Autoimmune lymphoproliferative syndrome Clinical manifestations Laboratory manifestations Pathophysiology ALPS-FAS ALPS-sFAS ALPS-FASL ALPS-CASP10 ALPS-U (formerly ALPS-III) Diagnostic criteria Required criteria Primary accessory criteria Secondary accessory criteria Treatment Prognosis Lymphomatoid papulosis in children Histology Treatment Prognosis Further reading and references 17 Myelodysplastic syndromes and myeloproliferative disorders Myelodysplastic syndromes Diagnostic criteria and classification Epidemiology Therapy-related myeloid neoplasms Pathophysiology Clinical features Cytogenetics Molecular genetics Differential diagnosis Prognosis Treatment Myeloid proliferations in children with Down syndrome (DS) Incidence Biology Treatment Treatment of transient abnormal myelopoiesis in Down syndrome Juvenile myelomonocytic leukemia Epidemiology Clinical features Laboratory features Blood smear Bone marrow Cytogenetics Genetics Differential diagnosis Biology Molecular genetic events Natural history Prognosis Treatment Hematopoietic stem cell transplantation Prehematopoietic stem cell transplantation approaches Targeted/investigational therapies Treatment options for patients with relapse after allogeneic HSCT Myeloproliferative neoplasms Chronic myeloid leukemia, BCR–ABL1 positive Introduction Epidemiology Clinical and laboratory features Advanced phases Accelerated phase Blast phase Diagnostic workup Treatment Initial selection of tyrosine kinase inhibitors Management of refractoriness and when to switch tyrosine kinase inhibitors Treatment of advanced stages Indication of allogeneic stem cell transplant Discontinuation of tyrosine kinase inhibitor Essential thrombocythemia and polycythemia vera Primary myelofibrosis Clinical features Hematologic findings Differential diagnosis Complications Genetic mechanisms Treatment Further reading and references 18 Acute lymphoblastic leukemia Incidence of ALL Etiology Genetic considerations Clinical features of ALL General systemic effects Hematologic effects arising from bone marrow invasion Clinical manifestations arising from lymphoid system infiltration Clinical manifestations of extramedullary invasion Central nervous system involvement Genitourinary tract involvement Renal involvement Gastrointestinal involvement Bone and joint involvement Skin involvement Cardiac involvement Lung involvement Diagnosis Laboratory studies Classification Morphology Light microscopy Immunology Acute leukemia of ambiguous lineage Cytogenetics and molecular genetics of ALL Prognostic factors Treatment Treatment of newly diagnosed ALL Treatment of B-lineage ALL Treatment of “low-risk” B-lymphoblastic leukemia Treatment of hypodiploid B-lymphoblastic leukemia Treatment of mature B-cell lymphoma/leukemia Treatment of T-cell ALL