Morphologic Classification

Morphological classification of AML was proposed by the FAB Cooperative Group in 1976,14 based on the morphological and cytochemical features of the blast cells. The original proposal was revised and expanded in 1985.58 Although widely accepted, the FAB classification of AML has been the subject of recent suggestions for revision.11,59 The FAB criteria identify two clinically significant types of AML: acute promyelocytic leukemia (M3) and acute myelomonocytic leukemia with abnormal eosinophils (M4eos); however, the remaining AML subtypes appear to be a cytogenetically and immunologically heterogeneous group of diseases. Cytogenetic evaluation of AML identifies numerous prognostically significant types of AML. These genetic abnormalities however, do not precisely correlate with FAB categories. Although morphologic subtyping is inadequate as a sole criteria in the classification of AML it should continue to serve as a template from which to build other more clinically and relevant categories.

The recently proposed WHO classification of acute myeloid leukemias is summarized in Table 14-4, which recognizes distinct entities defined by a combination of morphology and cytogenetic abnormalities. According to the WHO proposals AMLs can be divided into three groups: 1. chromosomal abnormalities associated with recurrent translocations [i.e., t(15;17), t(8;21), inv(16)] that are commonly seen in children and young adults; 2. chromosomal abnormalities similar to those which are associated with myelodysplastic syndromes (MDS) (complex chromosomal abnormalities with mainly loss of genetic material). These leukemias are associated with multilineage dysplasia of bone marrow cells. 3. AML cases without having chromosomal abnormalities or multilineage dysplasia.

The FAB standard in the diagnosis of AML has been 30 percent or more blast cells out of all nucleated cells. However, the WHO morphology committee11 recommended lowering the threshold for the diagnosis of AML from 30 to 20 percent by emphasizing that the survival of patients with 20 to 30 percent blasts have a prognosis similar to that of patients with greater than 30 percent blasts. It is also known that the 30 percent blast threshold is ineffective to separate MDS and low blast count AML cases that have cytogenetic abnormalities associated with de novo AML and absence of dysplasia.60 Differentiation of low blast cell count AML from MDS is based on cytogenetic data. Moreover, in 1989, Cason et al.61 proposed the term peripheral acute leukemia for patients with peripheral blast counts of 30 percent or more and bone marrow blast counts of less than 30 percent whose clinical and cytogenetic characteristics are compatible with de novo AML. This was incorporated into acute leukemia classification by the National Cancer Institute Sponsored Workshop62 in 1990.

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