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In acute lymphoblastic leukemia (ALL), the malignant clone arises from hematopoietic progenitors in the bone marrow or lymphatic system resulting in an increase of immature nonfunctioning leukemic cells. Infiltration of bone marrow leads to anemia, granulocytopenia, and thrombocytopenia with the clinical manifestations of fatigue, weakness, infection, and hemorrhage. These symptoms are more often the reason a patient first seeks medical advice rather than consequences of tumor bulk, such as lymph node enlargement, hepatosplenomegaly caused by leukemic infiltration, or symptoms of the central nervous system (meningeosis leukemica).
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ALL is the most frequent neoplastic disease in children with an early peak at the age of 3–4 years. The incidence in adults ranges from 0.7 to 1.8/100 000 per year, being somewhat higher in adolescents and young adults (AYAs), decreasing in adults, but increasing again in elderly people. Thus, Philadelphia chromosome–positive ALL (Ph+ ALL; BCR/ABL translocation) is observed in half of elderly B-lineage patients. The frequency of immunologic, cytogenetic, and genetic subtypes changes substantially with age.
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The etiology of acute leukemias is unknown. Internal and external factors influence the incidence of leukemia. Exposure to ionizing radiation or to chemicals, including prior chemotherapy, is associated with an increased risk of developing leukemia, more often observed in acute myeloid leukemia (AML). However, increasingly, secondary ALLs have been observed, particularly after cytostatic treatment with alkylating agents and topoisomerase inhibitors as treatment for primary tumors, most often for AML, myelodysplastic syndromes, or breast cancer.
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Patients with some rare congenital chromosomal abnormalities have a higher risk of development of acute leukemia (e.g., Klinefelter’s syndrome, Fanconi’s anemia, Bloom’s syndrome, ataxia-telangiectasia, and neurofibromatosis). Those with Down’s syndrome have a twentyfold increased incidence of leukemia; ALL is increased in childhood and AML at an older age.
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No direct evidence implicates viruses as a major cause of human acute leukemia. However, viruses are involved in the pathogenesis of two lymphoid neoplasias. In the endemic African type of Burkitt’s lymphoma, the Epstein-Barr virus, a DNA virus of the herpes family, has been implicated as a potential causative agent (see Chap. 194). Endemic infection with human T-cell leukemia virus I in Japan and the Caribbean has been shown to be an etiologic agent for rare cases of adult T-cell leukemia/lymphoma (see Chap. 201).
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DIAGNOSIS AND CLASSIFICATION
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The diagnosis of acute leukemia is first made by examination of the peripheral blood and bone marrow. For further classification of the leukemic blast cells, cytochemical stains, immunologic markers, and cytogenetic and molecular analysis are required. The immunologic markers are still the major criteria to subdivide into B-cell lineage or T-cell lineage ALL leukemias.
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Peripheral blood counts ...