Significance of FAB subclassification of "acute myeloid leukemia, NOS" in the 2008 WHO classification: analysis of 5848 newly diagnosed patients

Abstract

The World Health Organization (WHO) classifies acute myeloid leukemia (AML) via genetic, immunophenotypic, biological, and clinical features. Still, "AML, not otherwise specified (NOS)" is further subdivided based on morphologic criteria similar to those of the French-American-British (FAB) classification. We analyzed the relevance of this practice in patients with newly diagnosed "AML, NOS" with available FAB information undergoing curative-intent therapy in trials of 3 cooperative study groups (Dutch-Belgian Cooperative Trial Group for Hematology/Oncology [HOVON], UK Medical Research Council/National Cancer Research Institute [MRC/NCRI], and the US cooperative group Southwest Oncology Group [SWOG]) or at MD Anderson Cancer Center. Ignoring information on NPM1 and CEBPA, 5848 patients met criteria for "AML, NOS." After multivariate adjustment, FAB M0 was independently associated with significantly lower likelihood of achieving complete remission and inferior relapse-free and overall survival as compared with FAB M1, M2, M4, M5, and M6, with inconclusive data regarding M7. However, restricting attention to known NPM1(neg) patients, FAB M0 was no longer associated with worse outcomes; restricting attention to patients known to be NPM1(neg)/CEPBA(neg) (ie, honoring the provisional entities of "AML with mutated NPM1" and "AML with mutated CEBPA") did not affect this result. In conclusion, in the 2008 WHO classification scheme, FAB subclassification does not provide prognostic information for "AML, NOS" cases if data on NPM1 and CEBPA mutations are available.

Figure 1

Survival estimates in newly diagnosed patients with “AML, NOS.” Kaplan-Meier estimates of OS (A) of 5848 and RFS (B) of 4458 patients with “AML, NOS” based on WHO 2008 classification by individual FAB category. (C-D) Survival in patients with FAB M0 and M1-M6. Kaplan-Meier estimates of OS (C) and RFS (D) of patients with newly diagnosed “AML, NOS” based on WHO 2008 classification and subclassified as either FAB M0 or M1-M6; patients with FAB M7 were excluded from this analysis.

Figure 2

Survival estimates of NPM1^– and NPM1^–/CEBPA^– patients with newly diagnosed “AML, NOS.” (A-D) NPM1^– patients. OS (A) and RFS (B) of NPM1^– patients by individual FAB category. OS (C) and RFS (D) of NPM1^– patients subclassified as either FAB M0 or M1-M6; patients with FAB M7 were excluded from this analysis. (E-F) NPM1^–/CEBPA^– patients. OS (E) and RFS (F) of NPM1^–/CEBPA^– patients subclassified as either FAB M0 or M1-M6; patients with FAB M7 were excluded from this analysis.