Chapter 104. Acute and Chronic Myeloid Leukemia (Part 1)

Harrisons Internal Medicine Chapter 104. Acute and Chronic Myeloid LeukemiaAcute and Chronic Myeloid Leukemia: IntroductionThe myeloid leukemias are a heterogeneous group of diseases characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hematopoietic system. In 2006 the estimated number of new myeloid leukemia cases in the United States was 16,430. These leukemias comprise a spectrum of malignancies that, untreated, range from rapidly fatal to slowly growing. Based on their untreated course, the myeloid leukemias have traditionally been designated acute or chronic. ...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 1) Chapter 104. Acute and Chronic Myeloid Leukemia (Part 1) Harrisons Internal Medicine > Chapter 104. Acute and Chronic MyeloidLeukemia Acute and Chronic Myeloid Leukemia: Introduction The myeloid leukemias are a heterogeneous group of diseases characterizedby infiltration of the blood, bone marrow, and other tissues by neoplastic cells ofthe hematopoietic system. In 2006 the estimated number of new myeloid leukemiacases in the United States was 16,430. These leukemias comprise a spectrum ofmalignancies that, untreated, range from rapidly fatal to slowly growing. Based ontheir untreated course, the myeloid leukemias have traditionally been designatedacute or chronic. Acute Myeloid Leukemia Incidence The incidence of acute myeloid leukemia (AML) is ~3.7 per 100,000people per year, and the age-adjusted incidence is higher in men than in women(4.6 versus 3.0). AML incidence increases with age; it is 1.9 in individuals 65. A significant increase in AML incidence has occurredover the past 10 years. Etiology Heredity, radiation, chemical and other occupational exposures, and drugshave been implicated in the development of AML. No direct evidence suggests aviral etiology. Heredity Certain syndromes with somatic cell chromosome aneuploidy, such astrisomy 21 noted in Down syndrome, are associated with an increased incidence ofAML. Inherited diseases with defective DNA repair, e.g., Fanconi anemia, Bloomsyndrome, and ataxia telangiectasia, are also associated with AML. Congenitalneutropenia (Kostmann syndrome) is a disease with mutations in the granulocytecolony-stimulating factor (G-CSF) receptor and, often, neutrophil elastase thatmay evolve into AML. Myeloproliferative syndromes may also evolve into AML(Chap. 103). Germ-line mutations of CCAAT/enhancer-binding protein α (C/EBPα), runt-related transcription factor 1 (RUNX1), and tumor protein p53 (TP53)have also been associated with a higher predisposition to AML in some series. Radiation Survivors of the atomic bomb explosions in Japan had an increasedincidence of myeloid leukemias that peaked 5–7 years after exposure. Therapeuticradiation alone seems to add little risk of AML but can increase the risk in peoplealso exposed to alkylating agents. Chemical and Other Exposures Exposure to benzene, a solvent used in the chemical, plastic, rubber, andpharmaceutical industries, is associated with an increased incidence of AML.Smoking and exposure to petroleum products, paint, embalming fluids, ethyleneoxide, herbicides, and pesticides, have also been associated with an increased riskof AML. Drugs Anticancer drugs are the leading cause of therapy-associated AML.Alkylating agent–associated leukemias occur on average 4–6 years after exposure,and affected individuals have aberrations in chromosomes 5 and 7. TopoisomeraseII inhibitor–associated leukemias occur 1–3 years after exposure, and affectedindividuals often have aberrations involving chromosome 11q23.Chloramphenicol, phenylbutazone, and, less commonly, chloroquine andmethoxypsoralen can result in bone marrow failure that may evolve into AML. Classification The World Health Organization (WHO) classification (Table 104-1)includes different biologically distinct groups based on immunophenotype, clinicalfeatures, and cytogenetic and molecular abnormalities in addition to morphology.In contrast to the previously used French-American-British (FAB) schema, theWHO classification places limited reliance on cytochemistry. Since much of therecent literature and some ongoing studies use the FAB classification, adescription of this system is also provided in Table 104-1. A major differencebetween the WHO and FAB systems is the blast cutoff for a diagnosis of AML asopposed to myelodysplastic syndrome (MDS); it is 20% in the WHO classificationand 30% in the FAB. AML with 20–30% blasts as defined by the WHOclassification can benefit from approved therapies for MDS (such as decitabine or5-azacytidine) that were approved in the past by the Food and DrugAdministration (FDA) for marketing based on trials using the FAB criteria.