The New WHO Classification for Akute Myeloid Leukemias and Myelodysplastic Syndromes

Summary

Since 1976 the classification of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) have followed the FAB classification. Several parameters from methods like multi-parameter immunophenotyping, cytogenetics and molecular genetics add informative informations over the last 25 years for classification of AML and MDS. This led to the proposal of a new classification by the WHO in 1999. The WHO classification is based primarily on cytogenetic and molecular genetic data and proposes a hierarchical structure of several subgroups of AML and MDS. Further studies will validate these new subcategories with respect to clinical relevance and therapeutical decisions.

Since 1976 the FAB classification (Bennett et al. 1976, Bennett et al. 1985) has been used to classify acute myeloid leukemias (AML) and since 1982 the myelodysplastic syndromes have also been grouped according to a FAB proposal (Bennett et al. 1982). Several methods like immunophenotyping, cytogenetic analysis and molecular genetic investigations led to some new subcategories, (e.g. AML MO or AML M7). However, another classification like the MIC classification (MIC 1988) was not used in daily practice for the classification of AML and MDS.

In 1999 Harris et al. proposed a new WHO classification for AML. This follows a hierarchical clustering with the first subgroup defined by cytogenetic aberrations. Upfront the FAB category of MDS RAEB-T was removed and AML was defined as blasts in bone marrow above 20%. Following the IPSS data of MDS (Greenberg et al. 1997) makes clear that RAEB-T biology is very near or similar to AML. This is with respect to the survival rate as well as the treatment outcome. It therefore seems consistent to define AML with blasts over 20% in the bone marrow. Even from our cytogenetic data the profile of AML de novo and MDS RAEB-T is very similar (Fig. 1).

The new WHO proposal in the first subgroup defined four cytogenetically characterized subtypes of AML: They have recurrent cytogenetic translocations defined on the molecular level by leukemia specific fusion genes, a pathogenetic role of fusion genes is proven and the knowledge of some pathophysiological aspects led to specific treatment options (AML M3, M3v). These four subgroups of AML bear the four cytogenetic aberrations: t (8;21), t(15;17), inv (16)/t (16;16) or t(11) q(23) (Table 1).

In the second step the WHO proposal defined a subgroup of AML according to dysplastic features in the bone marrow. A category of patients without any dysplastic features and dysplasia in one cell lineage only was separated from patients showing dysplasia in two or three cell lineages (trilineage dysplasia). The latter two were called multi-lineage dysplasia patients.