|Betreff: Leukemia...ALL....see ref to electromagnetic radiation...neutropenia.......|
|Datum: Thu, 12 Oct 2006 14:48:28 EDT|
Acute Lymphoblastic LeukemiaLast Updated: July 11, 2006
|Synonyms and related keywords: acute lymphocytic leukemia, acute lymphatic leukemia, acute lymphoid leukemia, ALL, pediatric cancer, childhood cancer, childhood malignancy, inherited genetic syndromes, lymphoblastic leukemia, leukemia, leukemic blasts, T cell, T-cell ALL, B cell, B-lineage ALL, BCR-ABL, MLL, high-risk ALL, exposure to ionizing radiation, exposure to electromagnetic fields, allogeneic hematopoietic stem cell transplantation, HSCT, bone marrow failure, anemia, thrombocytopenia, neutropenia, petechiae, bleeding, lymphadenopathy, hepatosplenomegaly, bone pain|
|Author: Noriko Satake, MD, Clinical
Fellow, Department of Pediatric Hematology-Oncology, Mattel Children's
Hospital at University of California at Los Angeles
Coauthor(s): Kathleen Sakamoto, MD, Professor, Department of Pediatrics, Division of Hematology-Oncology and Pathology and Laboratory Medicine, Mattel Children's Hospital, David Geffen School of Medicine, University of California at Los Angeles
|Editor(s): Stephan A Grupp, MD, PhD, Director, Stem Cell Biology Program, Children's Hospital of Philadelphia; Assistant Professor, Department of Pediatrics, Division of Oncology, University of Pennsylvania; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Timothy P Cripe, MD, PhD, Associate Professor of Pediatric Hematology/Oncology, University of Cincinnati; Director, Translational Research Trials Office, Department of Pediatrics, Cincinnati Children's Hospital Medical Center; Samuel Gross, MD, Professor Emeritus, Department of Pediatrics, University of Florida, Clinical Professor, Department of Pediatrics, UNC, Adjunct Professor, Department of Pediatrics, Duke University; and Robert J Arceci, MD, PhD, King Fahd Professor of Pediatric Oncology, Director, Department of Oncology, Division of Pediatric Oncology, Johns Hopkins University School of Medicine|
|INTRODUCTION||Section 2 of 11|
Background: Acute lymphoblastic leukemia (ALL) is the most common malignancy diagnosed in children, representing nearly one third of all pediatric cancers. The annual incidence of ALL is about 30 cases per million people, with a peak incidence in children aged 2-5 years. Although a few cases are associated with inherited genetic syndromes, the cause of ALL remains largely unknown.
Many environmental factors (eg, exposure to ionizing radiation and electromagnetic fields, parental use of alcohol and tobacco) have been investigated as potential risk factors, but none has been definitively shown to cause lymphoblastic leukemia. Improvements in diagnosis and treatment have produced cure rates that now exceed 80%.
Further refinements in therapy, including the use of risk-adapted treatment protocols, may improve cure rates for patients at high risk while limiting the toxicity of therapy for patients with a low risk of relapse (see Risk classification). This article summarizes advances in the diagnosis and treatment of childhood ALL.
Pathophysiology: In ALL, a lymphoid progenitor cell becomes genetically altered and subsequently undergoes dysregulated proliferation and clonal expansion. In most cases, the pathophysiology of transformed lymphoid cells reflects the altered expression of genes whose products contribute to the normal development of B cells and T cells.
Leukemic blasts have long been thought to represent the clonal expansion of hematopoietic progenitors blocked during their differentiation at discrete stages of development. Recent data challenge this theory and suggest that leukemia arises from the stem cell that acquires features of differentiated cells. Although this observation may appear to be a subtle difference, it is important because it implies the need to eradicate the leukemic stem cell, and not just the differentiated blasts, to achieve a cure. Nevertheless, leukemic blasts provide large, uniform populations of cells for molecular and functional analyses.
ALL is generally thought to arise in the bone marrow, but leukemic blasts may be systemically present at the time of presentation. They may be present in the bone marrow, thymus, liver, spleen, lymph nodes, testes, and CNS.
Mortality/Morbidity: Despite overall improvements in outcome, the prognosis for patients whose leukemic blast cells carry the BCR-ABL fusion created by t(9;22) or the MLL genetic rearrangements created by translocations involving 11q23 is poor. Their estimated event-free survival (EFS) is only about 30%. Until recently, allogeneic hematopoietic stem-cell transplantation (HSCT) during the first remission was believed to be the only curative treatment option for these 2 groups of patients.
However, recent data indicate heterogeneity in each group. For example, outcomes may be good in patients whose leukemic blast cells are positive for BCR-ABL fusion and whose disease has a good initial response to prednisone. In 1 study, the estimated 4-year EFS for patients with a good response to prednisone was 55%, whereas that for patients with a poor response was 10% (Schrappe, 1998). Likewise, the estimated 4-year EFS for infants with MLL rearrangements and a good prednisone response was 41%, whereas it was only 9% in those with a poor response to prednisone.
Race: ALL occurs more frequently in Caucasians than in African Americans. The annual incidence of ALL in children and adolescents younger than 15 years in the Caucasian population is 33 per million, compared with 15 per million children and adolescents younger than 15 years in the African American population.
Sex: ALL occurs slightly more frequently in boys than in girls. This difference is most pronounced for T-cell ALL.
The incidence of ALL peaks in children aged 2-5 years.
|CLINICAL||Section 3 of 11|
History: Children with ALL generally present with signs and symptoms that reflect bone marrow infiltration and extramedullary disease. Because leukemic blasts replace the bone marrow, patients present with signs of bone marrow failure, including anemia, thrombocytopenia, and neutropenia. Clinical manifestations include fatigue and pallor, petechiae and bleeding, and fever. In addition, leukemic spread may manifest as lymphadenopathy and hepatosplenomegaly. Other signs and symptoms of leukemia include weight loss, bone pain, and dyspnea.
Signs or symptoms of CNS involvement, even when it occurs, are rarely observed at the time of the initial diagnosis. The signs and symptoms include headache, nausea and vomiting, lethargy, irritability, nuchal rigidity, papilledema. Cranial nerve involvement, which most frequently involves the seventh, third, fourth, and sixth cranial nerves, may occur. Also, leukemia can involve as intracranial or spinal mass, which causes numerous neurologic symptoms, most of which are due to nerve compression.
Physical: Physical findings in children with ALL reflect bone marrow infiltration and extramedullary disease. Patients present with pallor caused by anemia, petechiae, and bruising secondary to thrombocytopenia. They also have signs of infection because of neutropenia. In addition, leukemic spread may be seen as lymphadenopathy and hepatosplenomegaly.