Ciencias

Clinical Review Article

The Acute Leukemias
Prabhas Mittal, MD Kenneth R. Meehan, MD

lthough acute leukemias are generally evaluated and treated by hematologists, it is important for general internists to have an understanding of these diseases. Patients often present to their internist with vague symptoms such as fever, malaise, or lethargy. The physical examination and laboratoryevaluation provide clues to the diagnosis of acute leukemia. It is critical to distinguish these malignant diseases, which require rapid therapeutic intervention, from benign hematologic disorders. This article provides a general overview of the acute leukemias and highlights the underlying pathophysiology, clinical presentation, prognosis, and outcome.

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EPIDEMIOLOGY The acute leukemias aredivided into 2 categories, depending upon their cell of origin. Leukemia evolving from the myeloid/granulocyte cell line is called acute myelogenous leukemia (AML). Lymphocytic precursors give rise to acute lymphocytic leukemia (ALL). Each year in the United States, approximately 10,000 persons develop AML and 3000 develop ALL.1 AML is the most common type of acute leukemia in adults, accounting for 80%of new cases. AML is uncommon in children. The incidence increases steadily with age, with a sharp increase after 45 years. ALL is the most common malignant disease affecting children, accounting for approximately 30% of all childhood cancers.2 ALL has a bimodal age distribution, peaking in children between 3 and 5 years of age and again in persons older than 65 years. RISK FACTORS Thedevelopment of acute leukemia, whether AML or ALL, has been associated with potential etiologic factors (Table 1). The mechanisms whereby certain factors

predispose patients to develop leukemia are unclear. Some predisposing factors (eg, genetic syndromes, hematologic dyscrasias) may be associated with chromosomal mutations and thus activate certain oncogenes or damage the DNA repair mechanisms in thebody. A genetic predisposition is also demonstrated by the high concordance rate for the development of acute leukemia between identical twins. 2 Exposure to chemicals and chemotherapeutic agents also increases the risk for the development of leukemia later in life. Potential agents include benzene, petroleum products, pesticides, hair dyes, tobacco smoking, and ionizing radiation. Treatment withcertain chemotherapeutic agents, including alkylating agents and topoisomerase inhibitors, increases the risk of developing secondary leukemias. Certain viruses have also been shown to increase the risk of acute leukemia. The human T-cell leukemia virus 1 (HTLV-1) is associated with T-cell leukemia/ lymphoma, and Epstein-Barr virus is associated with acute B-cell ALL.2 CLASSIFICATION OF ACUTELEUKEMIAS The original classification scheme proposed by the French-American-British (FAB) Cooperative Group divides AML into 8 subtypes (M0 to M7) and ALL into 3 subtypes (L1 to L3). Although AML blasts evolve from common myeloid precursors, the 8 subtypes differ in degree of maturation (Table 2). The blasts characteristic of the subtype M0 are undifferentiated, whereas those characteristic of M1 to M4possess granulocytic

Dr. Mittal is a Senior Fellow, and Dr. Meehan is an Associate Professor of Medicine, Division of Hematology and Oncology, Bone Marrow Transplant Program, Georgetown University Medical Center, Vincent T. Lombardi Cancer Center, Washington, DC.

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Hospital Physician May 2001 37

Mittal & Meehan : Acute Leukemias : pp. 37 – 44

Table 1.Predisposing Factors for the Development of Acute Leukemia
Genetic syndromes Down syndrome Bloom syndrome Neurofibromatosis Ataxia telangiectasis Fanconi’s anemia Medications Alkylating agents Topoisomerase inhibitors Environmental exposures Hydrocarbons Benzene Radiation Hematologic conditions Myelodysplastic syndromes Viruses Epstein-Barr virus HTLV-1
HTLV-1 = human T-cell leukemia virus 1.

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