Classification of Acute Leukemias

A useful classification of acute leukemia must be reproducible, must impart understanding of leukemogenesis and clinical behavior, and (most importantly) be clinically relevant, which makes such a classification indispensable for designing and comparing clinical trials. Classification systems by their very nature may influence the design of treatment regimens and may even bias investigations of leukemogenesis. The discovery over 30 years ago that the acute lymphoid and acute myeloid leukemias differed in their responses to chemotherapeutic agents set the stage for the development of clinically useful classifications. The first of these was based on the morphologic features of leukemic blasts, with different groups of hematologists establishing their own terminology and diagnostic criteria. This lack of uniform nomenclature and hence comparable classifications posed a major obstacle to rapid progress in the treatment and understanding of leukemia pathobiology. The first internationally accepted classification of acute leukemia was proposed in 1976 by the French–American–British (FAB) Cooperative Group (1). The initial FAB classification was based solely on morphologic criteria that were subsequently refined in 1981 and 1985 (2–4). Unfortunately, the revisions largely ignored exciting immunologic and cytogenetic discoveries that were contributing to an improved understanding and better treatment designs in acute leukemia. The morphologic, immunologic, and cytogenetic (MIC) classification, introduced in 1988, was the first to recognize the usefulness of cytogenetics for identifying subgroups of acute leukemia (5,6). The MIC system recognized additional subgroups of acute leukemia not discernible in the FAB classification. Modifications of the FAB classification were also recommended by a National Cancer Institute-sponsored workshop in 1990 (7). Treatment of pediatric leukemia is one of the great successes of modern cancer therapy. Much of the success can be attributed to the recognition of important patient risk factors and the design of effective therapy for patients at high risk of treatment failure (8). Although they are still important, older risk factors based on a patient’s physical manifestations or hematologic and biochemical testing have been largely replaced by biologic features of the leukemic cell. Present risk assignments depend heavily on combined morphologic, immunologic, cytogenetic, and (more recently) molecular genetic studies. The recently introduced World Health Organization (WHO) classification takes into account morphologic and immunologic features plus well-studied, common nonrandom chromosomal abnormalities that clearly influence the laboratory and clinical features of 2