Acute Leukemias

Acute leukemia, now more accurately referred to as acute nonlymphocytic leukemia (ANLL), is the more common form of leukemia in adults. Acute lymphoblastic leukemia is predominantly a disease of children that accounts for approximately 20% of all acute leukemias in adults. ANLL occurs with increasing frequency with advancing age and frequently is preceded by a more chronic hematologic disorder. Multiple myeloma, polycythemia vera, paroxysmal nocturnal hemoglobinuria (PNH), chronic myeloid leukemia (CML), and the myelodysplastic syndromes all have a high propensity to culminate in acute leukemia. When acute leukemia follows these disorders, the prognosis is significantly poorer than de novo leukemia.

Clinical manifestations of the acute leukemias are similar regardless of the cell of origin (lymphocytic or myelogenous). Typically there is an abrupt onset of nonspecific complaints, including fatigue, anorexia, weight loss, and weakness. Hematologic abnormalities frequently lead to the presenting symptoms; thus, anemia contributes to fatigue, thrombocytopenia leads to bleeding and bruising, and lack of mature neutrophils can lead to serious infections and concomitant fevers. Those patients who evolve into AML from a preceding hematologic disorder tend to have a more chronic evolution in their symptoms. The presence of anemia, thrombocytopenia, and granulocytopenia with circulating blast cells are the hallmark of acute leukemia. The marrow, when examined, is hypercellular with a lack of differentiation and a predominance of blasts.

The etiology of the acute leukemias is not completely understood but is thought to be the result of multiple genetic aberrations to a clone of hematopoietic cells. Many genetic defects have been associated with both acute myelogenous leukemia and acute lymphocytic leukemia. These genetic defects tend to be chromosomal translocations and frequently when characterized have involved so-called oncogenes. Many of these abnormalities are thought to be etiologically involved in the evolution of leukemia.

Classification The acute leukemias are broken down into acute nonlymphocytic leukemia, of which there are seven types, and the acute lymphocytic leukemias, of which there are three types. The lymphocytic leukemias and their subtypes are differentiated from the nonlymphocytic leukemia by the combination of morphology, immunophenotype, and cytogenetics. In some cases, the distinction can be very difficult. Nonetheless, it is important because therapy is directly related to the cell of origin of the leukemia. The most characteristic morphologic features distinguishing acute nonlymphocytic from acute lymphocytic leukemias are the presence of Auer rods and peroxidase stain positivity, which defines the leukemia as acute nonlymphocytic.