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Pediatric Myeloid Leukemia, Myelodysplasia, and Myeloproliferative Disease

Acute Myelogenous Leukemia Acute myelogenous leukemia (AML) comprises a heterogeneous group of disorders characterized by the malignant clonal transformation of a hematopoietic stem or progenitor cell. In recent years, deeper understanding has been gained into the chromosomal changes and specific genetic mutations that precipitate this transformation. AML is a relatively rare disorder in children, with between 500 and 600 newly diagnosed patients in the United States…

Acute Lymphoblastic Leukemia

The acute leukemias of childhood are rare diseases that collectively represent about 30% of malignancies in children younger than age 15 years. Approximately 3000 new cases of childhood leukemia occur annually in the United States, 80% of which are acute lymphoblastic leukemia (ALL). Between the 1960s and 1990s, the prognosis for children with ALL improved dramatically. With current multiagent chemotherapy regimens, 80% to 90% of children…

Pediatric Surgical Oncology

Successful treatment of pediatric solid tumors requires collaborative management by the disciplines of surgery, oncology, and radiotherapy. Multimodal therapy achieves the highest rate of cure in many solid tumors and often minimizes long-term morbidity. Smooth collaboration provides optimal care. The role of the surgeon varies greatly depending on the primary tumor, its site, and the presence or absence of metastatic disease. Surgeons should be involved in…

Pediatric Radiation Oncology

Principles of Radiation Oncology Radiation oncology is an effective and often critical component of multidisciplinary cancer care for many childhood malignancies. The delivery of radiation for the pediatric population is highly complex because of the diversity of patients, tumor location, and biology. Additional concerns regarding the use of radiation for this patient population include a high likelihood of cure, coupled with the well-known and often lifelong…

Immunotherapy of Cancer

The role of the immune system in controlling cancer was subject to debate for decades, reflecting the limited understanding of the immune system at the time and the complexity of tumor immunology. However, over time a wealth of evidence from murine and human studies has demonstrated that the immune system can control cancer. Numerous animal models have demonstrated the ability of T cells to reject tumors,…

Cancer Chemotherapy for Pediatric Patients

In the past two decades we have seen substantial advances in the number of available chemotherapeutic agents to treat a variety of neoplastic diseases, as well as in the discovery and development of new anticancer drugs, while our understanding of the biology and genetics of cancer continues to grow. The tools at our disposal now include classes of molecules with highly distinct structures and innovative mechanisms…

Cytogenetic and Molecular Pathology of Pediatric Cancer

Cytogenetic and molecular analyses have provided pivotal biologic and clinical insights into pediatric neoplasia. It is increasingly evident that genetic assays of various types can provide essential diagnostic or prognostic information about pediatric solid tumors and hematologic malignancies ( Tables 45-1 to 45-3 ). In this chapter we offer an overview of the methods in use for the analysis of cytogenetic and molecular aberrations ( Table…

Targeted Therapies in Oncology

With the discovery of nitrogen mustard as an anticancer agent in the 1940s, medicinal and hence systemic cancer therapy became a reality. The identification and application of cytotoxic agents dominated the next 60 years of cancer treatment. The success of imatinib for BCR-ABL rearranged chronic myelogenous leukemia (CML), the dramatic responses seen in patients with BRAF -mutated melanoma and ALK rearranged non–small cell lung cancer to…

Genetics and Epigenetics of Childhood Cancers

The first scientific reports of childhood cancers such as Virchow glioma (neuroblastoma), Wilms tumor (nephroblastoma), and Ewing sarcoma provided a classification system based on organ involvement but shed little light on the natural causes of these diseases. Subsequent study of cancer cells and animal tumors, and in particular Boveri's analysis of cell mitoses and Rous' study of oncogenic viruses, revealed that cancer is at least in…

Genetic Predisposition to Cancer

It is currently estimated that 1% to 10% of children with cancer develop the disease due to an underlying genetic predisposition. Over the last 3 decades, there has been an explosion in knowledge regarding the heritable causes of cancer, including the discovery of many genes that when mutated in the germline significantly increase the risk for tumor formation in children. This knowledge has allowed for a…

Informatics

The first genome to be sequenced came at a cost of $100 million. Only 13 years later, the price for sequencing an entire genome is nearing $1000 ( Fig. 41-1 ). Rapid increases in the speed and complexity of genomic sequencing technologies, coupled with dramatically decreasing costs, have created an overwhelming array of platforms, methods, and informatics analysis algorithms. In many publications the authors assume the…

Epidemiology of Leukemia in Childhood

Leukemias of childhood are a highly heterogeneous group of diseases. In reviewing the descriptive and analytic epidemiology of these malignancies, we have, when possible, emphasized specific subgroups as defined by morphologic, cytogenetic, or molecular features. In selected instances, evidence indicates that specific subgroups of leukemia may have distinct causes and that molecular abnormalities associated with particular subgroups may be linked with specific causal mechanisms. In assessing…

Origins and Evolution of Pediatric Cancers

“Nothing in biology makes sense except in the light of evolution” was Dobzhansky's bold but persuasive claim, and nothing is as natural in biology as natural selection. It has been occurring for approximately 3 billion years whenever heritable traits vary in replicating populations, affecting the survival and reproductive fitness of molecules, unicellular or multicellular organisms, each in the face of environmental selective pressures. When complex multicellular…

Hematologic Manifestations of Systemic Diseases in Children of the Developing World

Diagnosis and management of hematologic disorders in children in developing countries pose a number of problems that are not encountered in advanced Western societies. Although all the conditions that have been described in this book are seen in these populations, their clinical features may be modified to a varying degree by the coexistence of malnutrition, chronic bacterial infection, or parasitic illness. Furthermore, many of the common…

Hematologic Manifestations of Systemic Diseases *

* This chapter is modified from the original chapter written by Dr. R. Alan B. Ezekowitz and includes material written by Dr. Samuel E. Lux, IV, with his permission. Evaluation of almost any patient who seeks medical attention, particularly in a hospital setting, includes the obligatory complete blood cell count. The vast majority of these patients do not have a primary hematologic problem. However, there are…

Transfusion Medicine

* Revised from a chapter in an earlier edition whose authors included David F. Friedman, Grace Kao, Richard M. Kaufman, and Leslie Silberstein. Transfusion medicine focuses on the administration of blood, blood components, and purified blood proteins to patients for therapeutic purposes. Red blood cells (RBCs) are the most frequently used blood component. In this chapter RBC transfusions are discussed first, and issues that pertain to…

Acquired Disorders of Hemostasis

Acquired Hemorrhagic Disorders Chapter 29 describes how the application of clinical skills forms the cornerstone for the assessment of a potential bleeding disorder. After confirming that a bleeding disorder is present through a comprehensive medical history and physical examination, the clinician should next address whether the condition is likely familial or acquired. This is sometimes difficult because some patients with mild underlying heritable hemostatic defects (e.g.,…

Acquired Platelet Defects

Platelets play a critical role in hemostasis. When the vascular endothelium is disrupted, platelets adhere to the subendothelium and initiate primary hemostasis. The details of normal platelet physiology and function are presented in Chapter 26 . Excessive bleeding occurs if primary hemostasis is abnormal because platelets are either deficient in number or defective in function. Acquired platelet defects, both quantitative and qualitative, are discussed in this…

Inherited Disorders of Thrombosis and Fibrinolysis

For many years, researchers suspected that hereditary coagulation defects underlie a large percentage of venous thromboembolic events that could not be attributed to identifiable acquired risk factors. Acquired risk factors for venous thrombosis consist of a heterogeneous group of conditions and clinical disorders with diverse and poorly understood prothrombotic mechanisms. With expanding scientific knowledge of the hemostatic mechanism and the regulatory role of natural anticoagulants, major…

Rare Hereditary Coagulation Factor Abnormalities

Rare bleeding disorders consist of inherited quantitative or functional deficiencies of factors I (fibrinogen), II, V, VII, X, XI, and XIII; combined factor deficiencies, particularly of factors V and VIII; inherited quantitative or functional deficiencies of vitamin K–dependent factors; and disorders of excessive fibrinolysis. Rare bleeding disorders constitute about 3% to 5% of all inherited bleeding disorders. Many of these disorders, which are variable in their…