Lanzkowsky's Manual of Pediatric Hematology and Oncology

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
	Infant leukemia
	Philadelphia-positive ALL
	Ph-like ALL
	Down syndrome and ALL
	Relapse in children with ALL
	Immunotherapy for ALL
	Central nervous system relapse
		Treatment
		Toxicity of CNS treatment
		Testicular relapse
	Long-term effects of ALL therapy
	Future drugs in ALL therapy
	Further reading and references
19 Acute myeloid leukemia
	Incidence and epidemiology
	Etiology and predisposing conditions
		Conditions predisposing to AML
	Clinical features
	Diagnostic and monitoring studies
		Laboratory studies
			Blood count and bone marrow
			Coagulation profile
			Chemistry panel and tumor lysis monitoring
		Cerebrospinal fluid
		Cardiac function assessment
		Infectious disease evaluation
	Classification of AML
		Immunophenotype of AML
		Molecular genetics of AML
	Supportive care
		General care
		Infectious complications and prophylaxis
		Transfusions
		Tumor lysis syndrome
		Hyperleukocytosis
		Cardiac toxicity
			Dexrazoxane cardioprotection
	The treatment of newly diagnosed AML
		Minimal residual disease
		Hematopoietic stem cell transplant for AML
	Prognosis of newly diagnosed AML
	Relapsed and refractory AML
	Novel therapeutic approaches
		Targeting CD33
		Targeting mesothelin
		Targeting CD123
		Small-molecule inhibitors
			Targeting KMT2A fusion
			Targeting menin
			Targeting DOT1L
			Targeting TP53
			Targeting dysregulated signaling pathways
			FLT3 inhibitors
			Proteasome/ubiquitin pathway inhibitors
		Other novel agents
			BCL-2 inhibitors (venetoclax)
		Epigenetic targets
			Methyltransferase inhibitors (i.e., azacytidine and decitabine)
			Histone deacetylase (HDAC) inhibitors (i.e., vorinostat and panobinostat)
		Chimeric antigen receptor T-cell immunotherapy in AML
		Use of killer immunoglobulin receptor-mismatched natural killer cells in HSCT
	Acute promyelocytic leukemia
		Treatment of APML
		Supportive care for patients with APML
			Differentiation syndrome
	AML special subgroups
		Infant AML
		Myeloid leukemia of Down syndrome
		Acute mixed lineage leukemia (acute leukemia of ambiguous lineage)
	Further reading and references
20 Hodgkin lymphoma
	Etiology and epidemiology
	Risk factors
		Familial Hodgkin lymphoma
		EBV-associated Hodgkin lymphoma
		Socioeconomic status and Hodgkin lymphoma
	Biology
	Pathology
		Macroscopic features
		Histology
			Immunophenotypic features
	Clinical presentation
		Constitutional B symptoms
		Peripheral lymphadenopathy
		Mediastinal adenopathy
		Pulmonary
		Spleen
		Bone
		Hematology and bone marrow
		Liver
		Kidney
		Nervous system
	Diagnostic evaluation and staging
		Diagnostic evaluation
		Staging
	Prognostic factors
	Treatment
		Surgery
		Chemotherapy
		Targeted agents and immunotherapy
		Radiation
		Treatment for refractory or recurrent disease
		Long-term complications
		Secondary malignancies
		Cardiac toxicity
		Pulmonary dysfunction
		Thyroid dysfunction
		Gonadal dysfunction and infertility
			Male gonadal toxicity
			Female gonadal toxicity
		Psychosocial and neurocognitive impairment
	Follow-up evaluations
		During therapy
		After completion of therapy
		Monitoring for long-term outcomes
	Further reading and references
	Web resources
21 Non-Hodgkin lymphoma
	Introduction
	Incidence and epidemiology
		Incidence
		Epidemiology
	Pathologic classification
	Clinical features
	Diagnosis
	Staging
	Prognosis
	Management
		Emergency treatment
		Chemotherapy
		Radiation therapy (RT)
			CNS prophylaxis
			Extracranial involved sites
			Rare, low-grade lymphomas
			Palliation or mass effect
			Refractory or relapsed disease
		Surgical therapy
	Non-Hodgkin Lymphoma Subtypes
		Lymphoblastic lymphoma (LL)
		Burkitt and diffuse large B-cell NHL (DLBCL)
		Primary mediastinal large B-cell lymphoma (PBML)
		Anaplastic large-cell lymphoma (ALCL)
		Rare pediatric NHL
		Relapse
	Further reading and references
22 Central nervous system tumors
	Pathology
		Supratentorial lesions
		Infratentorial lesions
		Ventricular lesions
		Molecular pathology of CNS neoplasms
	Clinical manifestations
		Intracranial tumors
			General signs and symptoms of intracranial tumors
		Spinal tumors
	Diagnostic evaluation
		Computed tomography
		Magnetic resonance imaging
		Magnetic resonance angiography
		Magnetic resonance spectroscopy
		Positron emission tomography
		Cerebrospinal fluid examination
		Bone marrow aspiration and bone scan
	Treatment
		Surgery
		Radiotherapy
		Chemotherapy
		High-dose chemotherapy with autologous stem cell rescue
	Specific CNS tumors
		Astrocytomas
			Low-grade astrocytomas (WHO grades I and II)
				Surgery
				Radiotherapy
				Chemotherapy
				Prognosis
				Recurrence
			High-grade astrocytomas (WHO grades III and IV)
				Surgery
				Radiotherapy
				Chemotherapy
		Gliomas
			Brainstem gliomas
				Surgery
				Radiotherapy
				Chemotherapy
				Prognosis
			Optic pathway gliomas
				Management
				Prognosis
			Glioma genomics
		Medulloblastoma
			Surgery
			Radiotherapy
			Chemotherapy
			Prognosis
			Relapsed medulloblastoma
			Molecular subgroups
				WNT tumors
				Sonic hedgehog tumors
				Group 3 tumors
				Group 4 tumors
		Ependymomas
			Surgery
			Radiotherapy
			Chemotherapy
			Prognosis
			Genomics
		Craniopharyngiomas
			Surgery
			Radiotherapy
			Chemotherapy
			Prognosis
		Intracranial germ cell tumors
			Surgery
			Radiotherapy
			Chemotherapy
			Prognosis
		Atypical teratoid/rhabdoid tumor
	Genetic syndromes related to brain tumors
		Neurofibromatosis type 1
		Neurofibromatosis type 2
		Li–Fraumeni
		Von Hippel–Lindau
		Tuberous sclerosis
		Turcot syndrome
		Gorlin syndrome
	Further reading and references
23 Neuroblastoma
	Epidemiology
	Predisposition
	Pathology and biology
	Clinical features
		Anatomic site
			Head and neck
			Chest
			Abdomen
			Pelvis
			Paraspinal area
			Lymph nodes
			Bone
			Brain
		Other symptoms
		Paraneoplastic syndromes
	Diagnosis and staging
		Staging systems
	Treatment modalities
		Surgery
		Radiation therapy
	Prognosis, risk stratification, and therapy
		Patients with lower risk localized disease
		Patients with INRG stage MS disease
		Intermediate-risk patients
			Treatment of intermediate-risk patients
				Chemotherapy
				Surgery
				Radiation therapy
		High-risk neuroblastoma
			Induction therapy
			Consolidation therapy
			Postconsolidation therapy
		Posttherapy monitoring
		Special treatment considerations
			Spinal cord compression
			Opsoclonus myoclonus ataxia syndrome
				Treatment
	Neuroblastoma in the adolescent and young adult
	Further reading and references
24 Renal tumors
	Wilms tumor
		Incidence
		Associated congenital anomalies
			WAGR syndrome
			Denys–Drash syndrome
			Beckwith–Wiedemann syndrome
			Screening of children with WAGR, Denys–Drash, and Beckwith–Wiedemann syndromes
		Signs and symptoms of Wilms tumor
		Diagnostic studies
		Staging system
		Pathology
			Anaplastic Wilms tumor
			Loss of heterozygosity as a prognostic factor for Wilms tumor
			Gain of chromosome 1q as a prognostic factor for Wilms tumor
		Treatment
			Surgery
			Treatment of tumors considered inoperable
			Radiation therapy
		Bilateral Wilms tumor
		Posttherapy follow-up
		Prognosis
		Treatment for recurrent Wilms tumor
			Standard-risk relapse
			High-risk relapse
			Very high risk of relapse
		Local control for patients with relapsed disease
	Nephroblastomatosis
	Congenital mesoblastic nephroma
	Clear cell sarcoma of the kidney
	Rhabdoid tumor of the kidney
	Renal cell carcinoma
	Further reading and references
25 Rhabdomyosarcoma and other soft-tissue sarcomas
	Incidence and epidemiology
	Pathologic and genetic classification
		Genetics of RMS
	Clinical features
		Primary sites
		Signs and symptoms
	Diagnostic evaluation
	Staging
		Staging for RMS
		Staging for NRSTS
	Prognosis
		Prognosis for RMS
		Prognosis for NRSTS
	Treatment
		Treatment for RMS
			General principles
			Local control
			Systemic control
			Surgery
			Radiotherapy
			Chemotherapy
			Standard treatment of RMS
		Treatment regimens by risk-adapted classification
			Low-risk group
				Radiation therapy
				Chemotherapy
			Intermediate-risk group
			High-risk group
		Treatment of NRSTS
	Follow-up after completion of therapy
		First year after completion of therapy
		Second and third years after completion of therapy
		Fourth and fifth years after completion of therapy
	Recurrent disease
		Treatment
	Future perspectives
	Further reading and references
26 Malignant bone tumors
	Osteosarcoma
		Epidemiology
		Pathology
		Clinical manifestations
		Diagnostic evaluation
		Treatment of localized osteosarcoma
			Surgery
			Chemotherapy
		Treatment of metastatic osteosarcoma at presentation
		Treatment of relapsed osteosarcoma
		Newer agents under investigation
		Posttreatment surveillance
		Prognosis
	Ewing sarcoma family of tumors
		Epidemiology
		Pathology
		Molecular genetics
		Clinical features
		Diagnostic evaluation
		Treatment of localized EFT
			Surgery
			Radiation
			Chemotherapy
		Treatment of metastatic EFT
		Treatment of relapsed EFT
		Prognosis
	Other bone tumors
		Chondrosarcoma
			Pathology
			Clinical features
			Diagnostic evaluation
			Treatment
			Posttreatment surveillance
		Giant cell tumor of bone
			Clinical features
			Diagnostic evaluation
			RANKL inhibition
	Further reading and references
27 Retinoblastoma
	Incidence
	Classification
		Laterality
			Unilateral tumors
			Bilateral tumors
		Genetics
			The two-hit hypothesis
			The RB1 gene
			Hereditable RB
			Nonhereditable RB
		Genetic counseling
			Prenatal diagnosis and further genetic counseling
			13q Deletion syndrome
	Risk for second malignant neoplasms
	Pathology
		Retinoblastoma
		Retinocytoma
	Clinical features
		Presenting signs and symptoms
	Differential diagnosis
		Pseudoretinoblastoma
	Patterns of spread
		Intraocular
		Extraocular
		Trilateral RB
	Diagnostic procedures
		Screening
		Diagnosis of intraocular RB
		Defining extent of disease
			Extraocular extent of the disease
	Classification
	Treatment
	Treatment of intraocular RB
		Enucleation
		Focal ophthalmic therapies
		Systemic chemotherapy
		Focal chemotherapy delivery routes, including intraarterial, intravitreal, and intracameral chemotherapy
			Intraarterial chemotherapy
			Intravitreal chemotherapy
			Intracameral chemotherapy
		Radiotherapy
			External beam radiotherapy
			Plaque radiotherapy
	Treatment of recurrent RB
	Treatment of extraocular RB
	Posttreatment management
		Disease-related follow-up
		Toxicity-related follow-up
		Future perspectives
	Further reading and references
28 Extracranial germ cell tumors
	Epidemiology
	Biology
	Histology
	Molecular characteristics
	Clinical features
	Diagnostic evaluation
		Tumor markers
	Staging and risk stratification
	Treatment
		Benign germ cell tumors
			Teratoma
			Mature teratoma
			Immature teratoma
		Teratoma with malignant germ cell elements
			Sacrococcygeal teratoma
				Treatment
					Surgery
					Chemotherapy
					Prognosis
		Ovarian teratoma
		Mediastinal teratoma
			Treatment
				Surgery
				Chemotherapy
			Prognosis
		Malignant germ cell tumors
		Surgical interventions
			Testicular tumors
				Prepubertal males
				Postpubertal males
			Ovarian tumors
			Extragonadal tumors
	Risk-stratified therapeutic approaches
		Low risk
			Testicular stage I tumors
			Ovarian stage I tumors
		Standard and poor risk
			Standard risk 1
			Standard risk 2
			Poor risk
	Relapsed and resistant germ cell tumors
	Further reading and references
29 Hepatic tumors
	Incidence
	Epidemiology
	Pathology
	Clinical features
	Diagnostic evaluation
	Staging and risk stratification
	Treatment
		Hepatoblastoma
			Surgery
			Chemotherapy
			Radiation
		Hepatocellular carcinoma
			Surgery
			Chemotherapy
		Liver transplantation
		Additional therapies
		Prognosis
	Further reading and references
30 Hematopoietic stem cell transplantation and cellular therapy
	Allogeneic stem cell transplantation
		Histocompatibility testing
		Donor selection
			Suggested strategy for donor selection and prioritization
			Secondary donor prioritization (after HLA matching prioritization)
	HSC sources, collection, and manipulation
		Bone marrow
		Peripheral blood stem cells
		Umbilical cord blood
	Graft manipulation postcollection
		ABO incompatibility
		Graft-versus-host disease
		Purging of malignant cells
	Medical evaluation of HSC donors
	Pretransplantation preparative regimens (conditioning)
		Commonly used conditioning regimens
			Leukemia
			Non-Hodgkin lymphoma
			Solid tumors
			Severe aplastic anemia
			Fanconi anemia
			Miscellaneous conditions
		Nonmyeloablative and reduced-intensity regimens
		Second transplantation regimens
	Engraftment
		Evidence of engraftment
		Factors associated with increased risk of graft failure
	Complications of HSCT
		Immunodeficiency
			Infections
				Cytomegalovirus
		Interstitial pneumonitis
		Pancytopenia
		Graft-versus-host disease
			GVHD prophylaxis
				Methotrexate (short course)
				Cyclosporine
				Tacrolimus
				Sirolimus
				Mycophenolate mofetil
				Methylprednisolone
			Acute GVHD
				Treatment
					Prophylaxis
					Therapy
			Chronic GVHD
				Limited (usually involving only one organ)
				Extensive
				Prognosis
				Overlap syndrome
				Treatment
		Sinusolidal obstruction syndrome (SOS) (formerly called venoocclusive disease (VOD))
			Clinical manifestations
			Predisposing factors
			Prevention
			Treatment
		Late sequelae of stem cell transplantation
	Recent advances in HSCT
		Minimal residual disease assessment pre-HSCT
		Gene and adoptive cell therapy for hematologic and oncologic conditions
		Cancer applications
			Chimeric antigen receptor-T-cells
		NK cells
		Dendritic cells–based vaccines
		Tumor-infiltrating lymphocytes
		TCR-engineered lymphocytes
		Noncancer gene therapy applications
	Outcomes
	Further reading and references
31 Management of oncologic emergencies
	Metabolic emergencies
		Hyperleukocytosis
			Clinical features
			Treatment
		Tumor lysis syndrome
			Prevention and management
			Renal dysfunction from tumor lysis
	Cardiothoracic emergencies
		Superior vena cava syndrome and superior mediastinal syndrome
			Etiology
			Clinical features
			Management
	Abdominal emergencies
		Evaluation and diagnosis of abdominal emergencies
		Typhlitis
			Etiology
			Diagnosis
			Treatment
		Perirectal abscess/fistula
			Management
	Renal emergencies
		Oliguria/anuria
			Differential diagnoses
			Evaluation
			Therapy
		Hypertension
			Definition
			Etiology
			Symptoms
			Treatment
	Neurologic emergencies
		Evaluation and diagnosis of neurologic emergencies
			Differential diagnosis
			Management
		Spinal cord compression
			Pathophysiology
			Clinical presentation
			Evaluation
			Treatment
	Endocrine emergencies
		Syndrome of inappropriate antidiuretic hormone secretion
			Etiology
			Clinical features
			Laboratory features of syndrome of inappropriate antidiuretic hormone secretion
			Treatment
		Hypercalcemia of malignancy
			Etiology
			Clinical features
			Treatment
		Adrenal insufficiency
			Etiology
			Clinical features
			Treatment
	Treatment-associated emergencies
		Anaphylaxis and hypersensitivity to chemotherapeutic agents
			Commonly implicated agents
			Presentation
			Treatment
		Differentiation syndrome
			Presentation
			Treatment
		Ifosfamide-associated encephalopathy
			Symptoms
			Treatment and prevention
		Cytokine release syndrome
			Treatments that can cause cytokine release syndrome
			Presentation
			Management
			Immune effector cell-associated neurotoxicity syndrome
	Further reading and references
32 Supportive care of patients with cancer
	Management of infectious complications
		Febrile neutropenia
			Management of FN
			Alterations in initial FN management
		Fungal infection
		Fever in the nonneutropenic oncology patient
		Infection prophylaxis
			Antibacterial prophylaxis
			Antifungal prophylaxis
			Pneumocystis jirovecii pneumonia prophylaxis
			Antiviral prophylaxis
			Preexposure prophylaxis
			Postexposure prophylaxis
			Suppressive therapy for viral infections
			Special considerations with SARS-CoV-2
		Hospital infection control practices
		Anticipatory guidance
	Recognition and management of nausea and vomiting
		Antiemetic agents
	Mucositis
		Prevention and treatment of oral mucositis
	Pain management
		Developmental issues in pediatric pain management
		Assessment of pain
		Treatment of pain
			Step 1 therapy: nonopioid analgesics
			Step 2 therapy: weak opioids
			Step 3 therapy: strong opioids
			Step 4 therapy: adjuvant modalities
		Procedural pain management in children with cancer
		Neuropathic cancer pain
		Complementary therapies
	Nutritional status of the oncology patient
		Nutrition assessment
		Nutrition intervention
		Nutrition and survivorship
	Utilization of hematopoietic growth factors
		Granulocyte colony-stimulating factors
		Erythropoietin
		Platelet growth factors
		Interleukin-11
		TPO-receptor agonists
	Management of acute radiation side effects
		Hematologic toxicity
		CNS complications
		Skin complications
		Oral mucositis
		Dysgeusia
		Xerostomia
		GI complications
		Pneumonitis
		Other organ toxicity
	Management of CVCs
		Types of CVCs
		Peripherally inserted central catheters
		External tunneled CVCs
		Implanted ports
		CVC complications
		Infection
		Occlusions
		Thrombotic occlusion
		Catheter-related thrombosis
		Catheter maintenance
	Posttreatment immunizations
	Palliative care
		End-of-life care
		Common symptoms at the end of life
		Treatment of end-of-life symptoms
		Palliative RT
		Palliative sedation therapy
		Multidisciplinary care
	Further reading and references
33 Evaluation, investigations, and management of late effects of childhood cancer
	Models of survivorship care
	Interventions and screening guidelines
	Organ system–specific late effects
		Musculoskeletal system
			Surgery
			Chemotherapy
			Radiation
			Screening and management
		Cardiovascular system
			Chemotherapy
				Anthracyclines
				Cyclophosphamide
			Radiation
			Screening and management
		Respiratory system
			Surgery
			Chemotherapy
				Bleomycin
				Nitrosourea
			Radiation
			Screening and management
		Central nervous system
			Surgery
			Chemotherapy
			Radiation
			Screening and management
		Endocrine system
			Surgery
			Chemotherapy
				Female gonadal function
				Male gonadal function
			Radiation
			Screening and management
			Thyroid dysfunction
			Anterior pituitary dysfunction
				Growth hormone deficiency
				Luteinizing and follicle-stimulating hormone deficiency
				Precocious puberty
				Thyroid-stimulating hormone deficiency
				Adrenocorticotropin deficiency
				Hyperprolactinemia
			Posterior pituitary dysfunction
		Genitourinary system
			Surgery
			Chemotherapy
			Radiation
			Screening and management
		Ocular system
			Chemotherapy
			Radiation
			Screening and management
		Auditory system
			Chemotherapy
			Radiation
			Screening and management
		Gastrointestinal system
			Chemotherapy
			Radiation
			Screening and management
		Immunologic system
		Obesity
		Second neoplasms
			Chemotherapy
				Epipodophyllotoxins
				Anthracyclines
				Alkylating agents
			Radiation
			Screening and management
		Transfusions
		Psychosocial issues
	Future considerations
	Further reading and references
34 Psychosocial factors impacting children with cancer and their families
	Time of diagnosis
	Treatment initiation
		Adjustment of parents and family
		Interventions to promote adaptation
	Illness stabilization
		School reentry
		Medical adherence
	During relapses and recurrences
	Treatment outcomes: the unsuccessful course
		Termination of cure-directed treatment
		Palliative and hospice care
		Bereavement
	Treatment outcomes: the successful course
		End of treatment
		Survivorship
	Conclusion
	Further reading and references
35 Pediatric blood banking principles and transfusion medicine practices
	Introduction
	Immunohematology
		Major blood groups
		Rhesus and minor blood groups
		Autoantibodies and alloantibodies
	Donor recruitment and testing
		Blood donor recruitment
		Infectious disease testing
		Directed donations
	Blood collection and processing
		Blood collection
		Preservative agents
	Blood products
		Red blood cells
		Platelets
		Granulocytes
		Plasma and plasma-derived products
			Plasma
			Cryoprecipitate
			Prothrombin complex concentrates
			Factor VIIa
		Whole blood
	Blood component modification and administration
		Leukoreduction
		Irradiation
		Washing
		Volume reduction
		Pathogen inactivation
	Transfusion reactions
		Hemolytic transfusion reactions
		Febrile nonhemolytic reactions
		Allergic reactions
		Transfusion-related acute lung injury, transfusion-associated circulatory overload and transfusion-associated dyspnea
		Sepsis
	Special populations
		Massive transfusion protocols
		Neonates and infants
			Red blood cells
			Platelets
		Hemoglobinopathies
	Therapeutic apheresis
	Patient blood management
		Patient blood management programs
		Blood avoidance programs
	Further reading and references
Appendix 1 Hematological reference values
	Fetal and cord blood hematologic value
	Red cell values and related serum values
	White cell values
	Platelet values
	Coagulation values
	Bone marrow cells
Index
Back Cover